cholecalciferol and Inflammation

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is an essential hormone in regulating calcium/phosphorous balance and in the pathogenesis of inflammation, insulin resistance, and obesity. The main forms of vitamin D, Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are converted into the active form (1,25-dihydroxyvitamin D) thanks to two hydroxylations in the liver, kidney, pancreas, and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased, and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity, and cardiovascular disease. It is interesting to note that several long-term studies also revealed an inverse correlation between vitamin D levels and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects. While some studies demonstrated improvements in insulin sensitivity, glucose, and lipid metabolism, others revealed no significant effect on glycemic homeostasis and inflammation. This review aims to provide insight into the molecular basis of the relationship between vitamin D, insulin resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

Topics: Anti-Inflammatory Agents; Cardiovascular Diseases; Cholecalciferol; Cytokines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Insulin; Insulin Resistance; Metabolic Syndrome; Obesity; Pregnancy; Vitamin D; Vitamin D Deficiency; Vitamins

The 100th anniversary of the discovery of vitamin D3 (VitD3) coincides with significant recent advances in understanding its mechanism of action along with accumulating knowledge concerning its genomic and nongenomic activities. A close relationship between VitD3 and the immune system, including both types of immunity, innate and adaptive, has been newly identified, while low levels of VitD3 have been implicated in the development of autoimmune thyroiditis (AIT). Active 1,25(OH)

Topics: Cholecalciferol; COVID-19; Hashimoto Disease; Humans; Inflammation; Thyroiditis, Autoimmune; Vitamin D; Vitamin D Deficiency; Vitamins

Evidence of synergic health effects of co-supplementation with vitamin D and probiotics is emerging. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statement, scientific databases and the grey literature were searched, and a narrative review and risk of bias assessment were conducted. Seven randomized controlled trials were included, which had low risk of bias. Six studies were double-blind, and once single-blind, extended over 6-12 weeks, and included 50-105 participants. Conditions explored included schizophrenia, gestational diabetes, type 2 diabetes and coronary heart disease, polycystic ovarian syndrome, osteopenia, irritable bowel syndrome (IBS), and infantile colic. Supplementation frequency was daily or bi-monthly, with mainly vitamin D3, and

Topics: Bifidobacterium; Cholecalciferol; Dietary Supplements; Dyslipidemias; Female; Humans; Inflammation; Insulin Resistance; Lactobacillus; Male; Mental Health; Probiotics; Randomized Controlled Trials as Topic; Streptococcus

Intradialytic exercise (IDE) is not yet a routine practice for hemodialysis patients, the lack of guidelines supporting it being a major reason. This systematic review and meta-analysis of aerobic IDE interventions examined the efficacy of IDE regarding quality of life (QOL), serum phosphorus, dialysis efficiency, inflammatory status, vitamin D3, parathyroid hormone, intake of phosphate binders, mortality and hospitalization rate.. Pubmed, Medline (Ovid), Embase (Ovid), Cochrane, and Cinahl (EBSCO) databases were searched to retrieve studies up to June 12, 2018. A manual reference search was also performed. Studies were included if they evaluated (a) aerobic IDE effect on at least one of our study parameters, (b) adult hemodialysis patients, (c) patients for > 1 month.. Twenty-two studies were retrieved (706 participants), of which 12 were eligible for meta-analysis. Aerobic IDE had a significant positive effect on the QOL physical component score (QOL-PSC) and on mental component score (QOL-MCS) of SF36, but not on serum phosphorus or Kt/V.. IDE incorporation into clinical practice has a significant positive effect on QOL-PSC and QOL-MCS. In the reviewed studies, IDE did not result in any health hazard in hemodialysis patients. Nevertheless, future research should assess the long-term effectiveness and safety of IDE. The limitations of this review include the lack of quality analysis of the studies, the limited number of studies that could be included in the meta-analysis, the diversity in the exercise intensity, duration and modality, and the limited data for several outcomes.. CRD42016052062.

Topics: C-Reactive Protein; Chelating Agents; Cholecalciferol; Exercise; Hospitalization; Humans; Inflammation; Parathyroid Hormone; Phosphorus; Quality of Life; Renal Dialysis; Renal Insufficiency, Chronic

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

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Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; 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YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Vitamin D deficiency occurs frequently in patients with cystic fibrosis (CF). Vitamin D is important for optimal mineralization of bone and may be important for other comorbidities commonly occurring in patients with CF. Vitamin D deficiency in patients with CF can arise from various causes including pancreatic exocrine insufficiency, lack of outdoor activity, and alterations of vitamin D metabolism. Due to fat malabsorption stemming from pancreatic insufficiency, higher oral doses of vitamin D are necessary to correct and maintain optimal vitamin D status in patients with CF. Recent studies have demonstrated that higher vitamin D status is associated with better lung function and that vitamin D therapy may help recovery from pulmonary exacerbations of CF. The mechanisms by which vitamin D may exert its beneficial actions in CF are unclear but likely related to the role vitamin D has in modulating the adaptive and innate immune response. Large randomized clinical studies to evaluate the potential role of vitamin D as adjunctive therapy in CF that goes beyond bone are necessary.

Topics: Bone Diseases; Cholecalciferol; Clinical Trials as Topic; Comorbidity; Cystic Fibrosis; Ergocalciferols; Humans; Inflammation; Lung; Randomized Controlled Trials as Topic; Respiratory Function Tests; Vitamin D; Vitamin D Deficiency

Obesity induced low-grade chronic inflammation disrupts proper immune and metabolic function. Vitamin D deficiency increases inflammation, which is associated with cardiometabolic risk. This systematic review examines the association between oral vitamin D (VD) supplementation and circulating inflammatory biomarkers and glycemic outcomes from randomized controlled trials (RCTs) of overweight and/or obese adults.. MEDLINE OVID, EMBASE and the Cochrane Central Register of Controlled Trials were searched according to a predefined protocol. Eligible RCTs included adults randomized to receive either oral VD or placebo. Two reviewers independently assessed RCTs for inclusion. Bias was assessed using the Cochrane Collaboration risk of bias tool. Mean differences were calculated comparing end-of-study sample means between the independent VD and placebo groups.. Eleven unique RCTs met inclusion criteria from a total of 3,383 identified citations, including 79 screened articles and 14 full text data extractions. Inflammatory and glycemic measures were reported in 7 and 10 RCTs, respectively. Most trial findings were non-significant with considerable heterogeneity in design, participants and outcomes. All but one trial was rated as either high or unclear risk of bias. Two RCTs reported significant changes in inflammatory biomarkers; however, the mean difference between groups was not statistically significant: C-reactive protein 0.19 mg/L (p = 0.88); Tumor Necrosis Factor -0.54 pg/ml (p = 0.20). Two other trials found significant mean differences in fasting plasma glucose -0.32 mmol/L (p = 0.03), Hemoglobin A1c -0.13% (p = 0.04), and Homeostatic Model Assessment -0.86 (p = 0.02) following VD supplementation.. Overall, there is no clear established benefit of VD supplementation on inflammatory biomarkers among overweight/obese adults. Baseline serum VD possibly influences the effect of VD repletion on inflammatory markers. Risk of bias was present in most studies, thus supporting the need for higher quality studies in this area to more conclusively understand the role VD supplementation has on inflammatory pathways.

Topics: Adult; Blood Glucose; C-Reactive Protein; Cholecalciferol; Humans; Inflammation; Obesity; Overweight; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha; Vitamin D Deficiency; Vitamins

Vitamin D is involved in mineral and bone homeostasis, immune responses, anti-inflammation, anti-infection, and cancer prevention. Vitamin D receptor (VDR) is a nuclear receptor that mediates most biological functions of 1,25(OH)(2)D(3) or vitamin D(3), the active form of vitamin D. Recently, vitamin D(3)-induced autophagy has been reported. Autophagy is a lysosome-mediated catabolic pathway classified into three different types: macroautophagy, microautophagy, and chaperone-mediated autophagy. Autophagy contributes to anti-aging, antimicrobial defense, and tumor suppression. The functions of autophagy overlap remarkably with those of vitamin D/VDR signaling. This review focuses on vitamin D(3), VDR, and macroautophagy in inflammation and infection. We place emphasis on the regulatory roles of vitamin D(3) on autophagy at different steps, including induction, nucleation, elongation to maturation, and degradation. We summarize the known molecular mechanisms of vitamin D/VDR signaling on autophagy homeostasis. The potential application of the insights gleaned from these research findings to anti-inflammation and anti-infection is also discussed.

Topics: Animals; Autophagy; Cholecalciferol; Communicable Diseases; Homeostasis; Humans; Inflammation; Receptors, Calcitriol

Constant exposure to a wide variety of microbial pathogens represents a major challenge for our skin. Antimicrobial peptides (AMPs) are mediators of cutaneous innate immunity and protect primarily against microbial infections. Cathelicidins were among the first AMPs identified in human skin and recent evidence suggests that they exert a dual role in innate immune defense: At first, due to their antimicrobial activity they kill pathogens directly. In addition, these peptides initiate a potent host response to infection resulting in cytokine release, inflammation and a cellular response. Disturbed cathelicidin expression and function was observed in several common inflammatory skin diseases, such as psoriasis where cathelicidin peptide converts inert self-DNA and self-RNA into an autoimmune stimulus. In atopic dermatitis decreased levels of cathelicidin facilitating microbial superinfections have been discussed. Furthermore, abnormally processed cathelicidin peptides induce inflammation and a vascular response in rosacea. Until recently, the molecular mechanisms underlying cathelicidin regulation were unknown. Recently, the vitamin D3 pathway was identified as the major regulator of cathelicidin expression. Consequently, vitamin D3 entered the spotlight as an immune modulator with impact on both innate and adaptive immunity. Therapies targeting vitamin D3 signaling may provide new approaches for infectious and inflammatory skin diseases by affecting both innate and adaptive immune functions.

Topics: Antigen Presentation; Autoimmune Diseases; Bacterial Infections; Blood Bactericidal Activity; Cathelicidins; Cholecalciferol; Gene Expression Regulation; Humans; Immunomodulation; Inflammation; Signal Transduction; Skin

Macrophages are involved in the immune and the inflammatory response. The deregulation of their physiological properties is associated with several pathologies such as atherosclerosis and some cancers. Cytokines action on this blood lineage modulates p21WAF1/CIP1 expression. It appears that this protein may play a role in the inflammation regulation through PPAR (peroxysome proliferator-activated receptors) transcription factors, strongly linked to lipid metabolism. It could also be involved in the control of the proliferation of monocytes/macrophages, even if these cells are classically described as devoided of any proliferative capacity.

Topics: Apoptosis; Cell Differentiation; Cell Division; Cholecalciferol; Cyclin-Dependent Kinase Inhibitor p21; Cytokines; Gene Expression Regulation; Hematopoietic Stem Cells; Humans; Inflammation; Lipid Metabolism; Macrophages; Models, Biological; Monocytes; Multipotent Stem Cells; Myelopoiesis; Peroxisome Proliferator-Activated Receptors; PPAR gamma; Signal Transduction; Tretinoin

There is a recent renewed interest in vitamin D metabolism and pathophysiology, due to its recent description as a hormone with a positive impact on global health rather than a strictly bone hormone: vitamin D could be a protective factor against infection, autoimmunity, cardiovascular morbidity, and cancer. By contrast, vitamin D deficiency appears to be increasingly frequent worldwide. We propose a review of these new aspects of vitamin D metabolism, with a focus on vitamin D status in a local pediatric cohort. There is an urgent need for revisiting current guidelines on vitamin D supplementation and for closely monitoring serum vitamin D in children with chronic diseases, i.e., at greater risk of cardiovascular impairment, bone morbidity, infectious disease, and acute inflammation.

Topics: Autoimmune Diseases; Bacterial Infections; Bone and Bones; Bone Density Conservation Agents; Bone Diseases; Cardiovascular Diseases; Child; Cholecalciferol; Evidence-Based Medicine; France; Global Health; Humans; Inflammation; Meta-Analysis as Topic; Neoplasms; Prevalence; Risk Factors; Virus Diseases; Vitamin D; Vitamin D Deficiency

Airway inflammation in asthma is characterized by activation of T helper type-2 (Th2) T cells, IgE production and eosinophilia. In many cases, this process is related to an inappropriate T cell response to environmental allergens, and other T cell-dependent pathways may also be involved (such as Th17). Regulatory T cells (Tregs) are T cells that suppress potentially harmful immune responses. Two major subsets of Treg are CD25(hi), Foxp3(+)Tregs and IL-10-producing Tregs. There is evidence that the numbers or function of both subsets may be deficient in patients with atopic allergic disease. Recent work has extended these findings into the airway in asthma where Foxp3 expression was reduced and CD25(hi) Treg-suppressive function was deficient. In animal models of allergic airways disease, Tregs can suppress established airway inflammation and airway hyperresponsiveness, and protocols to enhance the development, recruitment and function of Tregs have been described. Together with studies of patients and in vitro studies of human T cells, these investigations are defining potential interventions to enhance Treg function in the airway in asthma. Existing therapies including corticosteroids and allergen immunotherapy act on Tregs, in part to increase IL-10 production, while vitamin D3 and long-acting beta-agonists enhance IL-10 Treg function. Other possibilities may be enhancement of Treg function via histamine or prostanoid receptors, or by blocking pro-inflammatory pathways that prevent suppression by Tregs (activation of Toll-like receptors, or production of cytokines such as IL-6 and TNF-alpha). As Tregs can also suppress the potentially beneficial immune response important for controlling infections and cancer, a therapeutic intervention should target allergen- or site-specific regulation.

Topics: Adrenal Cortex Hormones; Allergens; Animals; Asthma; Cholecalciferol; Cytokines; Forkhead Transcription Factors; Humans; Immunotherapy; Infections; Inflammation; Lymphocyte Activation; Neoplasms; Receptors, Prostaglandin; T-Lymphocytes, Regulatory; Th2 Cells; Vitamins

The research projects of the European Forum on Antiphospholipid Antibodies are representative of how dynamic is this area of investigation. The present review is focused on the most recent projects of the Forum on the aetiopathogenic aspects of the antiphospholipid syndrome (APS). Studies on the genetic background of the APS are ongoing in order to better define the proximity between APS and full-blown systemic lupus erythematosus. However, the analysis of the polymorphisms of genes coding for inflammatory mediators may offer new information on the role of inflammatory processes in triggering thrombotic events as well as the whole susceptibility for developing the vascular manifestations. A systematic and wide detection of serological markers of infectious processes will give new insight on the role of infectious agents in favouring autoimmunity in APS. Owing to the well-known role of vitamin D(3) defect in autoimmune disease, the detection of vitamin plasma levels in APS patients will offer the rationale for a possible therapeutic supplementation. Additional projects are aimed to better characterize the diagnostic/prognostic value of antiphospholipid antibodies (aPL) by defining their epitope specificity and binding avidity. Pregnancy complications represent the obstetric side of APS. Research projects are focussed on the role of complement activation in placenta damage and on the potential ability of aPL to affect the fertility. Finally, a study has been planned in order to draw definitive conclusions on the associations between aPL and atherosclerosis.

Topics: Abortion, Spontaneous; Animals; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; beta 2-Glycoprotein I; Cholecalciferol; Europe; Female; Humans; Inflammation; Lupus Erythematosus, Systemic; Pregnancy; Risk Factors

Dendritic cells (DCs) are uniquely well equipped antigen (Ag)-presenting cells. Their classic function was thought to be that of potent initiators of innate and adaptive immunity to infectious organisms and other Ags (including transplanted organs). Evidence has emerged, however, that DCs have a central and crucial role in determining the fate of immune responses toward either immunity or tolerance. This dichotomous function of DCs, coupled with their remarkable plasticity, renders them attractive therapeutic targets for immune modulation. In transplantation, much recent work has focused on the ability of DCs to silence immune reactivity in an Ag-specific manner in the hope of preventing rejection and diminishing reliance on potentially harmful immunosuppressive agents. Experimental strategies have included in vivo targeting of DCs, as well as ex vivo generation of regulatory (or tolerogenic) DCs with subsequent reinfusion (i.e. cell therapy). Different approaches to 'program' DC toward tolerogenic properties include genetic (transgene insertion), biologic (differential culture conditions, anti-inflammatory cytokine exposure) and pharmacologic manipulation. Recent data suggest a promising role for pharmacologic treatment as a means of generating potent regulatory DCs and have further stimulated speculation regarding their potential clinical application. Herein, we discuss evidence that the potential of regulatory DC therapy is considerable and that there are compelling reasons to evaluate it in the setting of organ transplantation in the near future.

Topics: Animals; Antigen-Presenting Cells; Cell Lineage; Cholecalciferol; Cytokines; Dendritic Cells; Graft Rejection; Humans; Immune Tolerance; Inflammation; Organ Transplantation; Transplantation Immunology; Transplantation Tolerance

The pathogenesis and progression of wound-healing involve intricate pathways and numerous chemical mediators. This remains an area of intense study as undesirable results of this process, such as hypertrophic scars and keloids, can result in significant morbidity. These lesions are distinct in their characteristics, although they are similar in their distribution in patients with darker skin colors. There is a robust inflammatory mechanism behind the formation of hypertrophic scars and keloids. Furthermore, their development may be intimately related to vitamin D-3, which has been shown to be a powerful anti-inflammatory agent. This chemical is made in the skin, whose production is influenced by various factors of which the amount of melanin is a crucial one. More specifically, an increase in pigmentation has been shown to decrease the amount of vitamin D-3 synthesis in the skin. Thus, this paper proposes the hypothesis linking the propensity of inflammation and subsequent scarring in darker-skinned individuals to the reduced levels of vitamin D-3 production in their skin.

Topics: Black or African American; Cholecalciferol; Cicatrix, Hypertrophic; Humans; Incidence; Inflammation; Melanins; Skin Pigmentation; Wound Healing

Active vitamin D3 modulates epidermal growth, keratinization and inflammation, and various vitamin D3 analogues have been shown to be effective in the treatment of psoriasis. These analogues now provide a useful addition to the therapeutic modalities available for the treatment of psoriasis. Epidermal hyperproliferation, abnormal keratinization and inflammation are the well-established hallmarks of the psoriatic plaque. The aim of this review is to provide an update of information on the cell biological effects of vitamin D3, and the influence of vitamin D analogues on the pathomechanisms of psoriasis.

Topics: Animals; Cell Division; Cell Line; Cholecalciferol; Humans; Inflammation; Keratinocytes; Mice; Psoriasis; Rats; Receptors, Calcitriol; Signal Transduction

Many other mediators of inflammation or biochemical pathways must be involved in producing post-inflammatory hyper and hypopigmentation. Most of these mechanisms remain to be identified. We hope the ideas presented in this report stimulate some future investigation, the results of which will improve both our own understanding of the epidermis and the role of the melanocyte as an integral part of this important issue.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Cholecalciferol; Humans; Inflammation; Pigmentation Disorders; Prostaglandins

BACKGROUNDAdverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D3) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of healthy human adults, we investigated the clinical and molecular immunomodulatory effects of a single high dose of oral vitamin D3 on an experimentally induced chemical rash.METHODSSkin inflammation was induced with topical nitrogen mustard (NM) in 28 participants. Participant-specific inflammatory responses to NM alone were characterized using clinical measures, serum studies, and skin tissue analysis over the next week. All participants underwent repeat NM exposure to the opposite arm and then received placebo or 200,000 IU cholecalciferol intervention. The complete rash reaction was followed by multi-omic analysis, clinical measures, and serum studies over 6 weeks.RESULTSCholecalciferol mitigated acute inflammation in all participants and achieved 6 weeks of durable responses. Integrative analysis of skin and blood identified an unexpected divergence in response severity to NM, corroborated by systemic neutrophilia and significant histopathologic and clinical differences. Multi-omic and pathway analyses revealed a 3-biomarker signature (CCL20, CCL2, CXCL8) unique to exaggerated responders that is suppressed by cholecalciferol and implicates IL-17 signaling involvement.CONCLUSIONHigh-dose systemic cholecalciferol may be an effective treatment for severe reactions to topical chemotherapy. Our findings have broad implications for cholecalciferol as an antiinflammatory intervention against the development of exaggerated immune responses.TRIAL REGISTRATIONclinicaltrials.gov (NCT02968446).FUNDINGNIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)).

Topics: Adult; Cholecalciferol; Double-Blind Method; Exanthema; Humans; Inflammation; Treatment Outcome

Recently, our group identified increased platelet-mediated inflammation in type 2 diabetes (T2DM) patients, and it is a well-established risk factor for diabetes complications, particularly for the development of cardiovascular diseases (CVD). Furthermore, vitamin D is reported to play an important role in the modulation of platelet hyperactivity and immune function, although the effect of vitamin D on platelet-mediated inflammation is not well studied. Hence, we aimed to investigate the effect of vitamin D supplementation on platelet-mediated inflammation in T2DM patients.. Six months of vitamin D supplementation increases the serum vitamin D3 and total 25(OH)D levels from the baseline (. Our study results provide evidence that vitamin D supportive therapy may help to reduce or prevent the disease progression and cardiovascular risk in T2DM patients by suppressing oxidative stress and platelet-mediated inflammation.. Clinical Trial Registry of India: CTRI/2019/01/016921.

Topics: Cholecalciferol; Diabetes Mellitus, Type 2; Dietary Supplements; Humans; Inflammation; Vitamin D; Vitamins

Vitamin D insufficiency is common in patients suffering from end-stage renal disease (ESRD). In contrast, vitamin D supplementation could improve the status of ESRD patients (ESRDP). However, this effect's molecular mechanism is not fully understood. Therefore, this study aimed to assess vitamin D supplementation's impact on inflammation and oxidative signaling pathways in ESRDP. 104 ESRDP were divided into placebo (53) and vitamin D (51) groups. They were also categorized into four subgroups based on the severity of vitamin D deficiency. The dose of vitamin D3 (0.25-0.5mg/day) supplementation was determined based on plasma levels of calcium and parathyroid hormone (PTH). Vitamin D supplementation was performed for eight weeks. Serum levels of calcium, phosphorus, PTH, albumin, creatinine, ALP, and glomerular filtration along with antioxidant enzymes, malondialdehyde, and pro-inflammatory factors were measured. Moreover, the Nrf2 and NF-ĸB expression was evaluated in whole blood. According to the results, vitamin D supplementation improved the status of patients with ESRD significantly as compared with the placebo group (p<0.05). In addition, the expression of NF-ĸB and the serum levels of pro-inflammatory factors and malondialdehyde were significantly reduced. Finally, the expression of Nrf-2 and the serum of antioxidant enzymes were raised in the vitamin D group as compared with the placebo group (p<0.05). Vitamin D reduces clinical and metabolic symptoms in ESRDP by modulating gene expression (in oxidative stress and inflammation).

Topics: Antioxidants; Biomarkers; Calcium; Cholecalciferol; Dietary Supplements; Humans; Inflammation; Kidney Failure, Chronic; Malondialdehyde; NF-kappa B; Oxidative Stress; Parathyroid Hormone; Vitamin D; Vitamin D Deficiency; Vitamins

Background: The VITAL study was a nationwide, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial of vitamin D3 (2000 IU/day) and marine n-3 FAs (1 g/day) supplements. We recently reported that vitamin D supplementation with or without omega 3 fatty acids reduced autoimmune disease by 22% in the VITAL study. Objective: To investigate the effects of vitamin D3 and/or n-3 FAs on changes in systemic inflammatory biomarkers including pro- and anti-inflammatory cytokines over a 4-year period in the VITAL sub-cohort with in-person evaluations at the Center for Clinical Investigations (CCI) in Boston. Design: Serum levels of four inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6, interleukin-10, and tumor necrosis factor-α) were measured in a total of 2713 samples from those 1054 VITAL/CCI participants (aged 64.9 ± 6.5 years, 49% female, 84% white, and 9% black) at baseline, year 2, and year 4 follow-up visits. Results: In multiple-adjusted models, vitamin D3 supplementation decreased serum hs-CRP levels by 19% at 2-year follow-up (nominal p = 0.007; p-value after multiple comparison adjustment = 0.028), but not at 4-year follow-up (nominal and adjusted p-values > 0.05). The effects of vitamin D3 on other inflammatory markers were not statistically significant either at year 2 or year 4 (all adjusted p-values > 0.05). Marine n-3 FAs were not significantly associated with changes of all the above inflammatory markers either at years 2 and 4, after multiple comparison adjustment (all p-values > 0.05). Conclusions: Vitamin D3 supplementation with or without n-3 FAs decreased hs-CRP by 19% at year 2, but not other inflammatory biomarkers at year 2 or year 4, while n-3 FAs with or without vitamin D3 did not significantly affect these biomarkers at either time point. Our findings support a potential role of vitamin D supplementation in modulating the chronic inflammatory process, systemic inflammation, and possibly autoimmune disease progression.

Topics: Biomarkers; C-Reactive Protein; Cholecalciferol; Dietary Supplements; Double-Blind Method; Fatty Acids, Omega-3; Female; Humans; Inflammation; Male; Vitamin D

Procalcitonin is a biomarker of systemic inflammation and may have importance in the immune response. The metabolic response to elevated procalcitonin in critical illness is not known. The response to inflammation is vitally important to understanding metabolism alterations during extreme stress. Our aim was to determine if patients with elevated procalcitonin have differences in the metabolomic response to early critical illness. We performed a metabolomics study of the VITdAL-ICU trial where subjects received high dose vitamin D

Topics: Aged; Cholecalciferol; Critical Illness; Energy Metabolism; Female; Humans; Inflammation; Male; Metabolic Networks and Pathways; Metabolome; Metabolomics; Middle Aged; Placebo Effect; Procalcitonin; Vitamins

Seasonal variations have been reported for immune markers. However, the relative contributions of sunlight and vitamin D variability on such seasonal changes are unknown.. This double-blind, randomized, placebo-controlled trial tested whether daily 400 IU vitamin D. 62 subjects were randomized equally to vitamin D versus placebo in March and assessed at baseline, April (4w), June (12w), September (25w) and January (43w). Circulating nTregs,. Daily low dose Vitamin D intake did not affect the nTregs population. There were seasonal variation in nTregs, proliferative response and cytokines, suggesting that environmental changes influence immune response, but the mechanism seems independent of vitamin D status. Vitamin D attenuated the seasonal change in T cell-produced IFN-γ, suggesting a decrease in effector response which could be associated with inflammation.. https://www.isrctn.com, identifier (ISRCTN 73114576).

Topics: Adult; Cell Proliferation; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Interferon-gamma; Interleukin-10; Male; Middle Aged; Seasons; Sunlight; T-Lymphocytes, Regulatory

Due to anti-inflammatory effects of vitamin D3, we aimed to explore the effects of supplementation with this vitamin on headache characteristics and serum levels of pro/anti-inflammatory markers in migraineurs.. This placebo-controlled, double-blind study included 80 episodic migraineurs who randomly assigned into two equal groups to receive either daily dose of vitamin D3 2000 IU (50 μg) or placebo for 12 weeks. At baseline and after the trial, headache characteristics were determined using diaries and serum levels of interleukin (IL)-10, IL-6, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (Cox-2) were assessed via ELISA method.. At the end of trial, analysis of covariance (ANCOVA) adjusted for baseline values, and confounders revealed that vitamin D3 supplemented group experienced significantly lower headache days per month (4.71), reduced attacks duration (12.99 h/attack), less severe headaches (5.47, visual analog scale), and lower analgesics use/month (2.85) than placebo group (6.43, 18.32, 6.38 and 4.87, respectively) (P values < 0.05). Using ANCOVA adjusted for baseline levels and confounding variables, it was found that serum levels of IL-10 and Cox-2 did not significantly differ between groups after the experiment; whereas, iNOS serum level was significantly reduced in the intervention group (106.06 U/L) comparing to the controls (156.18 U/L P : 0.001). Also, the patients receiving vitamin D3 yielded a marginally significant lower IL-6 serum concentration (76.43 ng/L) compared to placebo (93.10 ng/L) (P value:0.055).. Based on the results of this study, we found that 2000 IU (50 μg)/day vitamin D3 supplementation for 12 weeks could improve headache characteristics and might reduce neuro-inflammation in episodic migraine.

Topics: Adult; Anti-Inflammatory Agents; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Headache; Humans; Inflammation; Inflammation Mediators; Male; Migraine Disorders; Treatment Outcome

This study examines the effects of vitamin D and omega-3 fatty acid co-supplementation on inflammation and nutritional status in colorectal cancer patients. Patients were randomly assigned into four groups: (1) controls, receiving placebos; (2) omega-3 fatty acid arm, receiving two 330 mg omega-3 fatty acid capsules daily and placebo (for vitamin D

Topics: Adjuvants, Pharmaceutic; Albumins; C-Reactive Protein; Cholecalciferol; Colonic Neoplasms; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Nutritional Status; Research Design; Tumor Necrosis Factor-alpha

This study aimed to evaluate the effects of vitamin D

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitriol; Chemotherapy, Adjuvant; Cholecalciferol; Colorectal Neoplasms; Dietary Supplements; Fatty Acids, Omega-3; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Nutritional Status; Tumor Necrosis Factor-alpha

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is more prevalent in women. Vitamin D deficiency and hormonal disorders are also prevalent in Iranian women, and may influence the severity of clinical outcomes mediated by microinflammation, oxidative stress and intestinal permeability pathways. Our objective was to investigate the effects of co-administration of soy and vitamin D on some inflammatory, antioxidant and gut permeability markers in women with IBS.. In a randomized clinical trial, women (18-75 years of age) were randomly allocated into four groups to receive soy isoflavones (40 mg/day), cholecalciferol (50,000 IU/15 days), both soy isoflavones and cholecalciferol, or placebo for six weeks. The outcomes were plasma inflammatory markers, antioxidant status and fecal protease activity at week 0 and week 6.. After the intervention, plasma inflammatory markers and fecal protease activity were reduced significantly in all treatment groups compared to the placebo group; however, there was no significant effect on antioxidant status.. This study suggests combined supplementation of soy isoflavones and active vitamin D can improve some biochemical parameters regarding inflammation and intestinal permeability of IBS in women.. Clinical.Trials.govNCT02026518.

Topics: Adolescent; Adult; Aged; Antioxidants; Biomarkers; Cholecalciferol; Dietary Supplements; Feces; Female; Gastrointestinal Tract; Humans; Inflammation; Iran; Irritable Bowel Syndrome; Isoflavones; Middle Aged; Permeability; Serine Proteases; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency; Young Adult

Soccer-induced muscle damage and inflammation lead to a reduction in athletic performance. The aim of this study was to determine whether supplementation with cholecalciferol would reduce inflammation and muscle damage in soccer players after a simulated soccer match.. Twenty-two soccer players (median age 27 y, interquartile range 5 y) were divided randomly into two groups, as follows: a cholecalciferol group (n = 11) and a placebo group (n = 11). Cholecalciferol supplements (50 000 IU/wk) or placebos were administered to the groups by an independent co-worker. After 8 wk, the athletes participated in a simulated soccer match, and perceived exertion and heart rates were measured during the trial. Blood samples were obtained presupplementation, postsupplementation, immediately after, and 2- and 24-h postexercise for measurement of lactate dehydrogenase, creatine phosphokinase, C-reactive protein (CRP), and interleukin (IL)-6.. The intervention group demonstrated a significant increase in serum 25-hydroxyvitamin D levels (53.93, 10.68 ng/mL, P < 0.0001), which is the best indicator of vitamin D levels in the body, with no change in the circulating markers of muscle damage and CRP (P ˃ 0.05) but showed increased IL-6 (P = 0.034). In addition, the ratings of perceived exertion and heart rates were not altered by vitamin D compared with placebo ingestion (P = 0.155 versus P = 0.261; P = 0.600 versus P = 0.983).. The study showed that 50 000 IU/wk of cholecalciferol supplementation for 8 wk increased the 25-hydroxyvitamin D levels, with no effect on muscle damage indices or CRP. However, The IL-6 concentration was generally higher in the intervention group.

Topics: Adult; Athletic Performance; Biomarkers; Body Mass Index; Cholecalciferol; Computer Simulation; Dietary Supplements; Double-Blind Method; Humans; Inflammation; Inflammation Mediators; Male; Muscle, Skeletal; Oxygen Consumption; Soccer; Vitamin D; Vitamins; Young Adult

Background: Low levels of vitamin D are found in a great part of breast cancer women. Study subjects using vitamin\ D3 supplement had lower rates of cancers and fewer markers of inflammation. Additionally, recent studies demonstrate\ the power of vitamin D supplementation to lower inflammation and oxidative stress biomarkers associate with VDR\ polymorphism to reduce inflammation. This study was aimed to assess the impact of vitamin D3 supplementation on\ the serum concentration of inflammatory markers and antioxidant capacity with regard to VDR polymorphism in the\ VDR gene in breast cancer women. Methods: A randomized, double-blind, placebo-controlled trial was conducted on 56\ breast cancer women. Participants were assigned to 2 treatment arms: placebo and vitamin D3 for 2 months intervention.\ Supplementation group received 50,000 IU of vitamin weekly. Blood samples were collected at baseline and after\ the intervention to measure the 25(OH) D3, TNF-α, TGF- β and TAC. Genotyping was performed for FokI, BsmI, ApaI,\ and TaqI polymorphism. Results: After eight weeks supplementation, the intervention group showed a significant increase\ in the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004 and TAC (48.9±13.3 to 63.5±13.3; p= 0.017).\ Changes in TNF-α, TGF- β1 were not significant. Serum TAC levels of participants with the TT/Tt, Ff genotypes were\ more responsive to supplementation. Conclusions: Supplementation with a vitamin D3 increased the TAC in breast\ cancer women, although it had no effect on inflammatory markers. Serum TAC in the TT/Tt, Ff were more responsive to\ vitamin D supplement compared with those with the FF/ff and tt genotypes.

Topics: Antioxidants; Biomarkers, Tumor; Breast Neoplasms; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Follow-Up Studies; Genotype; Humans; Inflammation; Middle Aged; Oxidative Stress; Polymorphism, Genetic; Prognosis; Receptors, Calcitriol; Vitamins

This study was conducted to evaluate the effects of vitamin D supplementation on the recurrence and metabolic status of patients with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3).. This randomized, double-blind, placebo-controlled trial was carried out among 58 women diagnosed with CIN2/3. Participants were randomly assigned into 2 groups to receive either 50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months.. The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly decreased fasting plasma glucose (-7.8 ± 9.2 vs. -1.1 ± 8.6 mg/dL, p = 0.006) and insulin levels (-3.2 ± 4.8 vs. -0.9 ± 3.4 µIU/mL, p = 0.03), and significantly increased quantitative insulin sensitivity check index (0.01 ± 0.02 vs. 0.002 ± 0.01, p = 0.02) compared with the placebo. Additionally, there was a significant decrease in high-sensitivity C-reactive protein (-815.3 ± 1,786.2 vs. 717.5 ± 1,827.3 ng/mL, p = 0.002) and a significant increase in total antioxidant capacity (113.4 ± 137.4 vs. -53.7 ± 186.7 mmol/L, p < 0.001) following the supplementation of vitamin D compared with the placebo.. Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence.

Topics: Adult; Antioxidants; C-Reactive Protein; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Insulin Resistance; Metabolome; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Oxidative Stress; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vitamins

Combined omega-3 fatty acid and vitamin D supplementation may improve multiple sclerosis (MS) by correcting metabolic abnormalities and attenuating oxidative stress and inflammation.. This study aimed to determine the effects of ω-3 fatty acid and vitamin D cosupplementation on the disability score and metabolic status of patients with MS.. This was a randomized, placebo-controlled clinical trial with Expanded Disability Status Scale (EDSS) score and inflammation as primary outcomes and oxidative stress biomarkers and metabolic profile as secondary outcomes. Patients, aged 18-55 y, were matched for disease EDSS scores, gender, medications, BMI, and age (n = 53) and randomly received a combined 2 × 1000 mg/d ω-3 fatty acid and 50,000 IU/biweekly cholecalciferol supplement or placebo for 12 wk. The placebos were matched in colour, shape, size, packaging, smell, and taste with supplements. Fasting blood samples were collected at baseline and end of intervention to measure different outcomes. Multiple linear regression models were used to assess treatment effects on outcomes adjusting for confounding variables.. Patients taking ω-3 fatty acid plus vitamin D supplements showed a significant improvement in EDSS (β -0.18; 95% CI: -0.33, -0.04; P = 0.01), compared with placebo. Serum high-sensitivity C-reactive protein (β -1.70 mg/L; 95% CI: -2.49, -0.90 mg/L; P < 0.001), plasma total antioxidant capacity (β +55.4 mmol/L; 95% CI: 9.2, 101.6 mmol/L; P = 0.02), total glutathione (β +51.14 µmol/L; 95% CI: 14.42, 87.87 µmol/L; P = 0.007), and malondialdehyde concentrations (β -0.86 µmol/L; 95% CI: -1.10, -0.63 µmol/L; P < 0.001) were significantly improved in the supplemented group compared with the placebo group. In addition, ω-3 fatty acid and vitamin D cosupplementation resulted in a significant reduction in serum insulin, insulin resistance, and total/HDL-cholesterol, and a significant increase in insulin sensitivity and serum HDL-cholesterol concentrations.. Overall, taking ω-3 fatty acid and vitamin D supplements for 12 wk by patients with MS had beneficial effects on EDSS and metabolic status. This trial was registered at the Iranian website (www.irct.ir) for registration of clinical trials as IRCT2017090133941N20.

Topics: Adult; Analgesics; Antioxidants; C-Reactive Protein; Cholecalciferol; Cholesterol; Cholesterol, HDL; Dietary Fats; Dietary Supplements; Disability Evaluation; Disabled Persons; Fatty Acids, Omega-3; Female; Glutathione; Humans; Inflammation; Insulin; Insulin Resistance; Malondialdehyde; Multiple Sclerosis; Oxidative Stress; Vitamins

Cardiovascular Disease (CVD) and related disorders remain a leading cause of health disparities and premature death for African Americans. Hypovitaminosis D is disproportionately prevalent in African Americans and has been linked to CVD and CVD risk factors including hypertension, diabetes and obesity. Thus, hypovitaminosis D may represent a common pathway influencing CV risk factors in a select subgroup of persons. The purpose of this paper is to report the study design of a prospective eight week prospective double-blind randomized, placebo-controlled trial (n = 330 allocated 2:1 to intervention vs. control) to assess the effect of placebo vs. high-dose oral cholecalciferol (100,000 IU vitamin D3 at baseline and week 2) on 6-week change of select biologic cardiometabolic risk factors (including parathyroid hormone to assess biologic activity, pro-inflammatory/pro-thrombotic/fibrotic markers, insulin sensitivity and vitamin D metabolites) and their relationship to vitamin D administration and modification by vitamin D receptor polymorphisms in overweight, hypertensive African Americans with hypovitaminosis D. Findings from this trial will present insights into potential causal links between vitamin D repletion and mechanistic pathways of CV disease, including established and novel genomic markers.

Topics: Black or African American; Cholecalciferol; Cytokines; Double-Blind Method; Humans; Hypertension; Inflammation; Insulin Resistance; Overweight; Parathyroid Hormone; Vitamin D Deficiency; Vitamin D-Binding Protein; Vitamins

The prevalence of Vitamin D deficiency is increasing worldwide, which has be shown to be associated with increased risk of cardiovascular disease (CVD), autoimmune disease, and metabolic syndrome. These conditions are also associated with a heightened state of inflammation. The aim of the current study was to evaluate the effect of vitamin D supplementation on serum C-Reactive Protein (CRP) level and Neutrophil-to-lymphocyte ratio (NLR) distribution in a large cohort of adolescent girls. A total of 580 adolescent girls were recruited follow by evaluation of CRP and hematological parameters before and after supplementation with vitamin D supplements as 9 of 50000 IU cholecalciferol capsules for 9 weeks taken at weekly intervals. At baseline, serum hs-CRP level was 0.9 (95%CI: 0.5-1.8), while this value after intervention was reduced to 0.8 (95%CI: 0.3-1.6; P = 0.007). Similar results were also detected for NLR (e.g., NLR level was 1.66 ± 0.72 and 1.53 ± 0.67, P = 0.002, before and after therapy with compliance rate of >95.2%). Moreover, we found an association between hs-CRP and BMI, triglyceride, white blood cell count, and lymphocytes. Interestingly we observed a significant reduction in neutrophil count and CRP level after high dose vitamin D supplementation. Our findings showed that the high dose supplementation of vitamin D affects measures of systemic inflammation: reductions in High Sensitivity C-Reactive Protein level and Neutrophil-to-lymphocyte ratio (NLR) distribution. J. Cell. Biochem. 118: 4317-4322, 2017. © 2017 Wiley Periodicals, Inc.

Topics: Adolescent; Body Mass Index; C-Reactive Protein; Child; Cholecalciferol; Female; Follow-Up Studies; Humans; Inflammation; Lymphocyte Count; Triglycerides; Vitamin D; Vitamin D Deficiency

The diverse immunomodulatory effects of vitamin D are increasingly being recognized. However, the ability of oral vitamin D to modulate acute inflammation in vivo has not been established in humans. In a double-blinded, placebo-controlled interventional trial, 20 healthy adults were randomized to receive either placebo or a high dose of vitamin D

Topics: Administration, Oral; Adult; Cholecalciferol; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Inflammation; Male; Middle Aged; Skin; Sunburn; Time Factors; Treatment Outcome; Vitamins; Young Adult

It has been reported that vitamin D regulates the immune system. However, whether vitamin D repletion modulates inflammatory responses in lymphocytes from dialysis patients is unclear. In the clinical trial, thirty-two (32) dialysis patients with 25 vitamin D ≤ 20ng/mL were randomized to receive either supplementation of cholecalciferol 100,000 UI/week/3 months (16 patients) or placebo (16 patients). In the in vitro study, B and T lymphocytes from 12 healthy volunteers (HV) were incubated with or without uremic serum in the presence or absence of 25 or 1,25 vitamin D. We evaluated the intracellular expression of IL-6, IFN-γ TLR7, TLR9, VDR, CYP27b1 and CYP24a1 by flow cytometry. We observed a reduction in the expression of TLR7, TLR9, INF-γ and CYP24a1 and an increase in VDR and CYP27b1 expression in patients which were supplemented with cholecalciferol, whereas no differences were found in the placebo group. Uremic serum increased the intracellular expression of IL-6, IFN-γ, TLR7, TLR9, VDR, CYP27b1 and CYP24a1. Treatment with 25 or 1,25 vitamin D decreased IL-6 and TLR9. CYP24a1 silencing plus treatment with 25 and/or 1,25 vitamin D had an additional reduction effect on IL-6, IFN-γ, TLR7 and TLR9 expression. This is the first study showing that cholecalciferol repletion has an anti-inflammatory effect and improves vitamin D intracellular regulatory enzymes on lymphocytes from dialysis patients.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Case-Control Studies; Cholecalciferol; Cytokines; Double-Blind Method; Humans; Inflammation; Inflammation Mediators; Pilot Projects; Placebos; Receptors, Calcitriol; Toll-Like Receptors; Uremia; Vitamin D; Vitamin D3 24-Hydroxylase

Cholecalciferol (vitamin D3) improves vascular function and inflammation, potentially providing an explanation for the proposed cardiovascular protection of vitamin D.. We investigated whether cholecalciferol supplementation reduces postprandial arterial dysfunction and inflammation.. Randomized, 1:1, double-blind trial.. Diabetes and Vascular Center, Franciscus Gasthuis, Rotterdam, The Netherlands.. Twenty-four healthy, premenopausal, overweight or obese, vitamin D-deficient women.. A single high (300,000 IU) or low dose (75,000 IU) of cholecalciferol.. The effect of low- and high-dose cholecalciferol on postprandial leukocyte activation markers, pulse wave velocity (PWV), and augmentation index (AIx) during an oral fat loading test, expressed as area under the curve (AUC).. High- and low-dose supplementation increased vitamin D by 163% ± 134% (P < 0.001) and 66% ± 59% (P < 0.001), respectively. Monocyte CD11b-AUC slightly increased after low but not high dose (6% ± 2%, P = 0.012, and 4% ± 1%, P = 0.339, respectively). There were no significant effects on postprandial PWV or AIx by high- or low-dose vitamin D. Fasting complement component 3 (C3) levels decreased by 5.9% (P = 0.004) in the high-dose group and by 4.0% (P = 0.018) in the low-dose group.. A single dose of vitamin D does not seem to reduce arterial stiffness and leukocyte activation in overweight, vitamin D-deficient women. Vitamin D may decrease fasting C3. Possibly, higher vitamin D concentrations may be needed to decrease inflammation and improve vascular function in overweight or obese vitamin D-deficient women.

Topics: Adult; Apolipoprotein A-I; Apolipoproteins B; Area Under Curve; C-Reactive Protein; Cholecalciferol; Cholesterol, HDL; Cholesterol, LDL; Complement C3; Double-Blind Method; Female; Humans; Inflammation; Leukocyte Count; Monocytes; Neutrophils; Obesity; Overweight; Postprandial Period; Pulse Wave Analysis; Triglycerides; Vascular Stiffness; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; 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Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; 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Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Little is known about the relationship between vitamin D deficiency and adolescents with type 1 diabetes. On the basis of adult studies showing that vitamin D improves insulin sensitivity and decreases inflammatory cytokines linked to microvascular complications, we hypothesized that treating vitamin D deficiency in adolescents with type 1 diabetes would improve glycemia and reduce inflammatory markers.. This was a randomized, prospective, crossover study of 25 adolescents with type 1 diabetes for at least a year (aged: 13-21 yr; 62% female; 62% Hispanic) and vitamin D deficiency (25-OH vitamin D ≤30 ng/mL). Subjects received vitamin D3 (20 000 IU/week) for 6 months, either immediately or after 6 months of observation.. At baseline, 63% of subjects screened were vitamin D deficient and randomized. Interleukin-6 (IL-6) was significantly higher in the vitamin D deficient group compared with the sufficient group (medians: 0.36 vs. 0.18) (p = 0.026), whereas neither C-reactive protein (CRP) nor tumor necrosis factor-α (TNF-α) differed. Vitamin D treatment increased serum levels of 25-OH vitamin D from 22 ± 5.3 to 34.3 ± 12.1 ng/mL (p < 0.01). However, treatment did not affect glycated hemoglobin (HbA1c), insulin dosage, CRP, interleukin-6 (IL-6), or TNF-α.. Vitamin D deficiency is prevalent in the adolescent type 1 diabetes population, and could be associated with changes in inflammatory markers. However, vitamin D repletion over 6 months did not affect glycemia or markers of inflammation in our study, highlighting the need for additional research to validate these findings.

Topics: Adolescent; Biomarkers; Blood Glucose; Cholecalciferol; Cross-Over Studies; Cytokines; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Female; Humans; Inflammation; Male; Prospective Studies; Vitamin D; Vitamin D Deficiency; Vitamins; Young Adult

Hypovitaminosis D and inflammation are highly prevalent among patients undergoing dialysis, and the association of both conditions with worse survival has been well recognized. Although a potential role for vitamin D in the immune system has been suggested, the effect of the treatment of hypovitaminosis D on the modulation of the inflammatory response remains unclear. The aim of this study was to investigate the effect of the restoration of the vitamin D status on the expression of vitamin D-regulatory proteins in monocytes and on circulating inflammatory markers in dialysis patients.. In this randomized double-blind placebo-controlled 12-week trial, 38 patients on dialysis with serum 25-hydroxyvitamin D [25(OH)D] <20 ng/mL were randomized either to the cholecalciferol group (n = 20; 50,000 IU of cholecalciferol twice weekly) or to the control group (n = 18; 50 drops of a placebo solution twice weekly). The expression of vitamin D receptor (VDR), CYP27B1, CYP24A1 and interleukin-6 (IL-6) in monocytes was determined by flow cytometry. Serum concentrations of 25(OH)D, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured. The trial is registered at ClinicalTrials.gov #NCT01974245.. After 12 weeks, the serum 25(OH)D increased from 14.3 ± 4.7 ng/mL to 43.1 ± 11.0 ng/mL (p < 0.05) in the cholecalciferol group and did not change in the control group (13.9 ± 4.2 ng/mL to 13.5 ± 4.3 ng/mL; p = 0.56). In monocytes, while CYP27B1 expression and VDR expression increased in the cholecalciferol group (p < 0.05), CYP27B1 expression did not change, and VDR expression decreased in the control group (p < 0.05). There were no changes in IL-6 and CYP24A1 expression in both groups. Serum concentration of IL-6 and CRP decreased from 8.1 ± 6.6 pg/mL to 4.6 ± 4.1 pg/mL (p < 0.05) and from 0.50 (0.10-1.27) mg/dL to 0.28 (0.09-0.62) mg/dL (p < 0.05), respectively only in the cholecalciferol group. Assessed overtime, the treatment group differences in 25(OH) D, PTH, CRP and IL-6, CYP27B1 and VDR remained significant.. Restoration of vitamin D status of patients undergoing dialysis promoted upregulation of CYP27B1 and VDR expression in monocytes and a decrease in circulating inflammatory markers.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Adult; Aged; Biomarkers; Brazil; C-Reactive Protein; Cholecalciferol; Double-Blind Method; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Monocytes; Placebos; Receptors, Calcitriol; Renal Dialysis; Vitamin D; Vitamin D Deficiency; Vitamin D3 24-Hydroxylase

Vitamin D deficiency is widespread in pregnancy and has been associated with adverse health conditions in mothers and infants. Vitamin D supplementation in pregnancy may support the maintenance of pregnancy by its effects on innate and adaptive immunity.. We assessed the effects of vitamin D supplementation during pregnancy on vitamin D status and markers of immune function associated with adverse pregnancy outcomes.. We conducted a randomized, controlled, double-blind intervention of 2 doses of cholecalciferol (400 and 2000 IU/d) from <20 wk to delivery in 57 pregnant women. Vitamin D status, regulatory and inflammatory T cells, markers of innate immunity and systemic inflammation, and clinical outcomes including maternal blood pressure and birth weight were assessed at 26 and 36 wk of pregnancy.. Supplementation with 2000 IU/d is more effective at increasing vitamin D status in pregnant women than 400 IU/d and is associated with increased regulatory T cell immunity that may prevent adverse outcomes caused by excess inflammation. This trial was registered at clinicaltrials.gov as NCT01417351.

Topics: Adult; Biomarkers; CD4-Positive T-Lymphocytes; Cholecalciferol; Cytokines; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Inflammation; Interleukin-10; Pregnancy; Toll-Like Receptors

Low 25-hydroxyvitamin D levels are common in patients with chronic fatigue syndrome; such patients also manifest impaired vascular health. We tested whether high-dose intermittent oral vitamin D therapy improved markers of vascular health and fatigue in patients with chronic fatigue syndrome.. Parallel-group, double-blind, randomised placebo-controlled trial. Patients with chronic fatigue syndrome according to the Fukuda (1994) and Canadian (2003) criteria were randomised to receive 100,000 units oral vitamin D3 or matching placebo every 2 months for 6 months. The primary outcome was arterial stiffness measured using carotid-femoral pulse wave velocity at 6 months. Secondary outcomes included flow-mediated dilatation of the brachial artery, blood pressure, cholesterol, insulin resistance, markers of inflammation and oxidative stress, and the Piper Fatigue scale. As many as 50 participants were randomised; mean age 49 (SD 13) years, mean baseline pulse wave velocity 7.8 m/s (SD 2.3), mean baseline office blood pressure 128/78 (18/12) mmHg and mean baseline 25-hydroxyvitamin D level 46 (18) nmol/L. 25-hydroxyvitamin D levels increased by 22 nmol/L at 6 months in the treatment group relative to placebo. There was no effect of treatment on pulse wave velocity at 6 months (adjusted treatment effect 0.0 m/s; 95% CI -0.6 to 0.6; p = 0.93). No improvement was seen in other vascular and metabolic outcomes, or in the Piper Fatigue scale at 6 months (adjusted treatment effect 0.2 points; 95% CI -0.8 to 1.2; p = 0.73).. High-dose oral vitamin D3 did not improve markers of vascular health or fatigue in patients with chronic fatigue syndrome.. www.controlled-trials.com, ISRCTN59927814.

Topics: Adult; Biomarkers; Blood Pressure; Brachial Artery; Canada; Cardiovascular Physiological Phenomena; Cholecalciferol; Cholesterol; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Fatigue Syndrome, Chronic; Female; Humans; Inflammation; Insulin Resistance; Male; Middle Aged; Oxidative Stress; Pulse Wave Analysis; Treatment Outcome; Vascular Stiffness; Vitamin D Deficiency

This study aimed to evaluate the effect of vitamin D3 megadose supplementation and influence of BsmI polymorphism in the VDR gene on the inflammatory profile and oxidative stress in elderly women with vitamin D deficiency.. A double blind, randomized, placebo-controlled trial was conducted with 40 elderly women (aged 68±6 years) diagnosed with vitamin D insufficiency (24.7±3.1 ng/mL). Participants were distributed into a supplementation group that received 200,000 IU of vitamin D3 (SG; n=20) and a placebo group (PG; n=20). Blood samples were collected at baseline and after intervention to analyse the 25(OH)D, parathyroid hormone, serum calcium, ultra-sensitive C-reactive protein (us-CRP), alpha 1-acid glycoprotein (AGP-A), total antioxidant capacity (TAC), and malondialdehyde (MDA) levels, as well as the renal and hepatic function, and genotyping was performed for BsmI polymorphism.. Four weeks after supplementation, elderly women in the SG group showed a significant increase in the serum concentration of 25(OH)D (25.29±2.8 to 31.48±6.0; p=0.0001), which was followed by increased TAC (65.25±15.66 to 71.83±10.71; p=0.03) and decreased serum PTH (46.32±13.2 to 35.45±11.0; p=0.009), us-CRP (0.38±0.3 to 0.19±0.1; p=0.007) and AGP-A levels (75.3±15.4 to 61.1±5.9; p=0.005). Changes in BP, ANAC and MDA were not observed. The 25(OH)D and PTH, us-CRP and AGP-A levels of participants with the BB/Bb genotype were more responsive to supplementation, but their other markers did not change.. Supplementation with a vitamin D3 megadose reduced inflammatory markers and increased the total antioxidant capacity in elderly women with vitamin D insufficiency. The 25(OH)D, PTH, us-CRP and AGP-A levels of elderly patients with the BB/Bb genotype were more responsive to supplementation compared with those with the bb genotype.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcium; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Genotype; Humans; Inflammation; Middle Aged; Oxidative Stress; Parathyroid Hormone; Polymorphism, Genetic; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency

Obesity and vitamin D deficiency are associated with risk for several cancers, possibly through inflammation and adipokine-related pathways. Two hundred and eighteen postmenopausal women with BMI > 25 kg/m(2) and low serum 25-hydroxyvitamin D (25(OH)D; ≥10-<32 ng/mL), were randomized to 12 months of either (i) weight-loss intervention + 2000 IU/day oral vitamin D3 or (ii) weight-loss intervention + daily placebo. Serum adiponectin, leptin, TNFα, IL6, IL1β, IL8, and IL10, were measured by immunoassay, and a composite inflammatory biomarker score calculated. Using generalized estimating equations, mean changes in outcomes were compared between arms (intent-to-treat), adjusted for possible confounders. Analyses were also stratified by weight-loss (gained/no weight-loss; <5%; 5% to 10%; ≥10%). At 12 months, there were no significant differences in analyte changes between arms. In stratified analyses, participants randomized to vitamin D3 who lost 5% to 10% of baseline weight, versus participants who gained weight/had no weight-loss, had significantly greater decreases in levels of IL6 compared with those randomized to placebo: absolute change -0.75 pg/mL (-17.2%), placebo versus -1.77 pg/mL (-37.3%), vitamin D, P = 0.004. Similar but attenuated results were observed for participants who lost ≥10% of baseline weight: -0.41 pg/mL (-13.6%), placebo versus -0.67 pg/mL (-17.3%), vitamin D, P = 0.02. Effects of vitamin D3 supplementation on levels of IL1β were inconsistent when stratified by weight loss. There were no intervention effects on IL10, TNFα, IL8, the composite score, adiponectin, or leptin, when stratified by weight-loss. In conclusion, vitamin D3 supplementation in combination with weight-loss of at least 5% of baseline weight was associated with significant reductions in levels of IL6.

Topics: Aged; Biomarkers; Cholecalciferol; Dietary Supplements; Female; Humans; Inflammation; Interleukin-6; Middle Aged; Obesity; Postmenopause; Weight Loss

Observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels are associated with inflammatory markers. Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups. Thus, we aimed to determine the effect of supplementary vitamin D using secondary data from a population-based, randomised, placebo-controlled, double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84-year-old residents of one of the four eastern states of Australia. They were randomly selected from the electoral roll and were randomised to one of three trial arms: placebo (n 214), 750 μg (n 215) or 1500 μg (n 215) vitamin D3, each taken once per month for 12 months. Post-intervention blood samples for the analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels were available for 613 participants. Associations between intervention group and biomarker levels were evaluated using quantile regression. There were no statistically significant differences in distributions of CRP, leptin, adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group and either supplemented group. The 75th percentile IL-6 level was 2·8 pg/ml higher (95 % CI 0·4, 5·8 pg/ml) in the 1500 μg group than in the placebo group (75th percentiles:11·0 v. 8·2 pg/ml), with a somewhat smaller, non-significant difference in 75th percentiles between the 750 μg and placebo groups. Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation, we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels, with the possible exception of IL-6.

Topics: Adipokines; Adiponectin; Aged; Biomarkers; C-Reactive Protein; Cholecalciferol; Cytokines; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Leptin; Male; Middle Aged; Vitamin D; Vitamin D Deficiency; Vitamins

The endothelium is important not only in regulating vascular tone but also in modulating inflammation. Patients with systemic lupus erythematosus (SLE) have deficits in these endothelial functions. Vitamin D is a nuclear hormone that regulates vascular endothelial nitric oxide synthase activity and expression. Many SLE patients have insufficient levels of vitamin D. The effect of this hormone on vascular endothelial function in SLE patients is not known. This study was designed to determine the effect size of repleting vitamin D levels on endothelial function in patients with SLE and vitamin D deficiency.. SLE patients with 25(OH) vitamin D (25(OH)D) levels <20 ng/mL were randomized to oral vitamin D3 (D3) doses that did or did not raise 25(OH)D levels to ≥32 ng/mL. Endothelial function was measured with flow-mediated dilation (FMD) before and after 16 weeks of vitamin D3 supplementation.. Half of those who achieved 25(OH)D levels of ≥32 ng/mL experienced increases in FMD, whereas none of those with continued low 25(OH)D levels did. Those with increases in FMD had significantly higher final 25(OH)D levels. Using the effect size from this study, future studies designed to test the effect of repleting 25(OH)D on FMD in vitamin D-deficient SLE patients will require 35 patients in each group.. These results suggest a potential role for vitamin D in SLE-related endothelial dysfunction and that an adaptive, multi-arm, treat-to-target, serum-level trial design may increase the efficiency and likelihood of success of such a study.

Topics: Administration, Oral; Adult; Cholecalciferol; Dietary Supplements; Endothelium; Female; Humans; Inflammation; Lupus Erythematosus, Systemic; Male; Middle Aged; Pilot Projects; Vascular Diseases; Vitamin D Deficiency

Observational studies have suggested that vitamin D may reduce inflammation in relapsing-remitting multiple sclerosis (RRMS), but this has not been clearly confirmed in randomized controlled trials. To further explore the possible anti-inflammatory effects of vitamin D in RRMS, we examined the effect of high-dose oral vitamin D3 on eleven markers of systemic inflammation in 68 RRMS patients enrolled in a double-blinded randomized placebo-controlled trial of vitamin D3 supplementation (20,000 IU/week) (NCT00785473). Serum inflammation markers and 25-hydroxyvitamin D (25(OH)D) were measured at baseline and week 96, and no restrictions were set on additional standard immunomodulatory treatment for RRMS. The mean 25(OH)D level rose from 56 ± 29 to 123 ± 34 nmol/L among patients receiving vitamin D3 supplementation, whereas only a minor increase from 57 ± 22 to 63 ± 24 nmol/L was seen in the placebo group. However, no significant differences appeared between the vitamin D group and the placebo group for any of the inflammation markers. Patients on immunomodulatory therapy had significantly higher levels of interleukin-1 receptor antagonist and chemokine (C-X-C motif) ligand 16 than patients without immunomodulatory treatment, but there were no clear synergistic effects between immunomodulatory therapy and vitamin D3 supplementation on any of the inflammation markers. The rise in 25(OH)D levels after vitamin D3 supplementation was unaffected by immunomodulatory treatment. We conclude that in this study of RRMS patients, high-dose oral vitamin D3 supplementation prominently increased serum 25(OH)D levels without affecting markers of systemic inflammation, while a more anti-inflammatory phenotype was found among patients on immunomodulatory treatment.

Topics: Adult; Biomarkers; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Treatment Outcome; Vitamin D; Young Adult

African Americans have a disproportionate burden of inflammation-associated chronic diseases such as cancer and lower circulating levels of 25-hydroxyvitamin D [25(OH)D]. The effect of vitamin D3 (cholecalciferol) supplementation on inflammatory markers is uncertain. We conducted a randomized, double-blind, placebo-controlled trial of supplemental oral vitamin D (placebo, 1,000, 2,000, or 4,000 IU/day of vitamin D3 orally for 3 months) in 328 African Americans (median age, 51 years) of public housing communities in Boston, MA, who were enrolled over three consecutive winter periods (2007-2010). Change from 0 to 3 months of plasma levels of 25(OH)D, high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-10, and soluble TNF-α receptor type 2 (sTNF-R2) in 292 (89%) participants were measured. Overall, no statistically significant changes in CRP, IL-6, IL-10, and sTNF-R2 were observed after the vitamin D supplementation period. Baseline CRP was significantly inversely associated with the baseline 25(OH)D level (P < 0.001) in unadjusted and adjusted models. An interaction between baseline 25(OH)D and vitamin D supplementation was observed for outcome change in log CRP (month 3-month 0; P for interaction = 0.04). Within an unselected population of African Americans, short-term exposure to vitamin D supplementation produced no change in circulating inflammatory markers. This study confirms the strong independent association of CRP with 25(OH)D status even after adjusting for body mass index. Future studies of longer supplemental vitamin D3 duration are necessary to examine the complex influence of vitamin D3 on CRP and other chronic inflammatory cytokines for possible reduction of cancer health disparities in African Americans.

Topics: Adult; Biomarkers; Black or African American; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Inflammation; Inflammation Mediators; Male; Middle Aged; Placebos; Vitamin D Deficiency

Memory T-cells are mediators of transplant injury, and no therapy is known to prevent the development of cross-reactive memory alloimmunity. Activated vitamin D is immunomodulatory, and vitamin D deficiency, common in hemodialysis patients awaiting transplantation, is associated with a heightened alloimmune response. Thus, we tested the hypothesis that vitamin D3 supplementation would prevent alloreactive T-cell memory formation in vitamin D-deficient hemodialysis patients.. We performed a 12-month single-center pilot randomized, controlled trial of 50,000 IU/week of cholecalciferol (D3) versus no supplementation in 96 hemodialysis patients with serum 25(OH)D<25 ng/mL, measuring effects on serum 25(OH)D and phenotypic and functional properties of T-cells. Participants were randomized 2:1 to active treatment versus control. D3 supplementation increased serum 25(OH)D at 6 weeks (13.5 [11.2] ng/mL to 42.5 [18.5] ng/mL, p<0.001) and for the duration of the study. No episodes of sustained hypercalcemia occurred in either group. Results of IFNγ ELISPOT-based panel of reactive T-cell assays (PRT), quantifying alloreactive memory, demonstrated greater increases in the controls over 1 year compared to the treatment group (delta PRT in treatment 104.8+/-330.8 vs 252.9+/-431.3 in control), but these changes in PRT between groups did not reach statistical significance (p = 0.25).. D3 supplements are safe, effective at treating vitamin D deficiency, and may prevent time-dependent increases in T-cell alloimmunity in hemodialysis patients, but their effects on alloimmunity need to be confirmed in larger studies. These findings support the routine supplementation of vitamin D-deficient transplant candidates on hemodialysis and highlight the need for large-scale prospective studies of vitamin D supplementation in transplant candidates and recipients.. Clinicaltrials.gov NCT01175798.

Topics: Administration, Oral; Cholecalciferol; Dietary Supplements; Female; Humans; Immunity, Cellular; Inflammation; Male; Middle Aged; Monocytes; Phenotype; Pilot Projects; Renal Dialysis; Safety; T-Lymphocytes; Time Factors

Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory autoimmune disease. Vitamin D has potent immunomodulatory properties that support its use in the treatment of autoimmune conditions, including SLE. We assessed vitamin D status in patients with SLE and determined alterations in inflammatory and hemostatic markers and disease activity before and after vitamin D supplementation.. Patients with SLE (n = 267) were randomized 2:1 to receive either oral cholecalciferol 2000 IU/day or placebo for 12 months. Outcome measures included assessment of alterations in levels of proinflammatory cytokines and hemostatic markers, and improvement in disease activity before and after 12 months of supplementation. Disease activity was measured by the SLE Disease Activity Index. Vitamin D levels were measured by Liaison immunoassay (normal 30-100 ng/ml). Serum levels between 10 and 30 ng/ml were classified as vitamin D insufficiency and levels < 10 ng/ml as vitamin D deficiency.. The mean 25(OH)D level at baseline was 19.8 ng/ml in patients compared to 28.7 ng/ml in controls. The overall prevalence of suboptimal and deficient 25(OH)D serum levels among patients with SLE at baseline was 69% and 39%, respectively. Lower 25(OH)D levels correlated significantly with higher SLE disease activity. At 12 months of therapy, there was a significant improvement in levels of inflammatory and hemostatic markers as well as disease activity in the treatment group compared to the placebo group.. Vitamin D supplementation in patients with SLE is recommended because increased vitamin D levels seem to ameliorate inflammatory and hemostatic markers and show a tendency toward subsequent clinical improvement. Clinical Trial Registry NCT01425775.

Topics: Adult; Biomarkers; Cholecalciferol; Cytokines; Double-Blind Method; Female; Humans; Inflammation; Lupus Erythematosus, Systemic; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Vitamin D has anti-inflammatory and immune-regulating properties. We aimed to determine if high-dose cholecalciferol supplementation for 1 year in subjects with early chronic kidney disease (CKD) improved circulating markers of inflammation and immunity.. In this double-blind, randomized, placebo-controlled trial, 46 subjects with early CKD (stages 2 and 3) were supplemented with oral cholecalciferol (50 000 IU weekly for 12 weeks followed by 50 000 IU every other week for 40 weeks) or a matching placebo for 1 year. Serum tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein-10 and neutrophil gelatinase-associated lipocalin were measured at baseline, 12 weeks and 1 year. Serum cathelicidin (LL-37) was measured at baseline and 12 weeks. An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide (LPS) and Pseudomonas aeruginosa.. By 12 weeks, serum MCP-1 decreased in the cholecalciferol group (66.2±2.5 to 60.8±2.6 pg/ml, group-by-time interaction P=0.02) but was not different from baseline at 1 year. Other markers of inflammation and immunity did not change. In vitro, LPS- and Pseudomonas-activated monocytes treated with 1,25(OH)2D3 had significantly less MCP-1 secretion compared with untreated cells.. High-dose cholecalciferol decreased serum MCP-1 concentrations by 12 weeks in patients with early CKD, although the decrease was not maintained for the remainder of the year. In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents; Antimicrobial Cationic Peptides; Biomarkers; Cathelicidins; Chemokine CCL2; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Immunity; Inflammation; Interferon-gamma; Interleukin-6; Male; Middle Aged; Renal Insufficiency, Chronic; Tumor Necrosis Factor-alpha; Vitamin D

We examined the effects of progressive resistance training (PRT) and supplementation with calcium-vitamin D(3) fortified milk on markers of systemic inflammation, and the relationship between inflammation and changes in muscle mass, size and strength. Healthy men aged 50-79 years (n = 180) participated in this 18-month randomized controlled trial that comprised a factorial 2 × 2 design. Participants were randomized to (1) PRT + fortified milk supplement, (2) PRT, (3) fortified milk supplement, or (4) a control group. Participants assigned to PRT trained 3 days per week, while those in the supplement groups consumed 400 ml day(-1) of milk containing 1,000 mg calcium plus 800 IU vitamin D(3). We collected venous blood samples at baseline, 12 and 18 months to measure the serum concentrations of IL-6, TNF-α and hs-CRP. There were no exercise × supplement interactions, but serum IL-6 was 29% lower (95% CI, -62, 0) in the PRT group compared with the control group after 12 months. Conversely, IL-6 was 31% higher (95% CI, -2, 65) in the supplement group compared with the non-supplemented groups after 12 and 18 months. These between-group differences did not persist after adjusting for changes in fat mass. In the PRT group, mid-tibia muscle cross-sectional area increased less in men with higher pre-training inflammation compared with those men with lower inflammation (net difference ~2.5%, p < 0.05). In conclusion, serum IL-6 concentration decreased following PRT, whereas it increased after supplementation with fortified milk concomitant with changes in fat mass. Furthermore, low-grade inflammation at baseline restricted muscle hypertrophy following PRT.

Topics: Animals; Biomarkers; Calcium, Dietary; Cholecalciferol; Dietary Supplements; Exercise; Food, Fortified; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Milk; Muscle Strength; Muscle, Skeletal; Physical Endurance; Resistance Training; Tumor Necrosis Factor-alpha

Epidemiological studies indicate a relation between vitamin D status and autoimmune diseases, and in vitro studies demonstrate an effect of 1,25-dihydroxyvitamin D on immune activation. However, the relation between serum levels of 25-hydroxyvitamin D (25(OH)D) and the effect of vitamin D supplementation on serum levels of cytokines are not settled. In the present study interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, intercellular adhesion molecule-1, interferon-gamma, monocyte chemotactic protein-1, and high sensitivity C-reactive protein, were measured in 437 overweight subjects and 324 completed a one year intervention with 40,000 IU vitamin D per week (group DD), 20,000 IU vitamin D per week (group DP), or placebo (group PP). No consistent relations between serum levels of the cytokines and 25(OH)D were found at baseline. In the intervention study, there was no difference in delta values (value at end of study minus value at inclusion) between the three groups regarding the individual cytokines measured, nor was there any indication of a polarization of the T cells towards a Th2 dominant type. In conclusion, we were not able to demonstrate with certainty any significant relation between serum levels of 25(OH)D levels and a number of cytokines and markers of inflammation.

Topics: Adult; Aged; Biomarkers; Cholecalciferol; Cross-Sectional Studies; Cytokines; Dietary Supplements; Female; Humans; Inflammation; Male; Middle Aged; Obesity; Smoking; Vitamin D; Young Adult

Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation.. This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m(2); aged >or=18 on entry to study; and serum 25-hydroxyvitamin D levels <75 nmol/L. Patients will be randomised 1:1 to receive either oral cholecalciferol 2000IU/day or placebo for 6 months. The primary outcome will be an improvement in insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp. Secondary outcome measures will include serum parathyroid hormone, cytokines (Interleukin-1beta, Interleukin-6, Tumour Necrosis Factor alpha), adiponectin (total and High Molecular Weight), osteocalcin (carboxylated and under-carboxylated), peripheral blood mononuclear cell Nuclear Factor Kappa-B p65 binding activity, brachial artery reactivity, aortic pulse wave velocity and waveform analysis, and indirect calorimetry. All outcome measures will be performed at baseline and end of study.. To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation between vitamin D status with supplementation, insulin resistance and markers of adverse cardiovascular risk. We remain hopeful that cholecalciferol may be a safe intervention, with health benefits beyond those related to bone-mineral homeostasis.. Australian and New Zealand Clinical Trials Registry ACTRN12609000246280.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Bone Density Conservation Agents; Cholecalciferol; Double-Blind Method; Female; Humans; Inflammation; Insulin Resistance; Kidney Failure, Chronic; Male; Placebo Effect; Treatment Outcome; Vitamin D Deficiency; Young Adult

Low levels of 25-hydroxyvitamin D [25(OH)D] are frequent in chronic kidney disease and are associated with adverse outcomes. The aim of this 5-year prospective study was to evaluate the effects of cholecalciferol supplementation on mineral metabolism, inflammation and cardiac parameters in hemodialysis (HD) patients.. The study included 97 patients. Cholecalciferol was given after HD according to 25(OH)D baseline levels measured twice (end of winter and of summer). The 25(OH)D levels, circulating bone metabolism, inflammation parameters, brain natriuretic peptide (BNP), pulse pressure (PP), and left ventricular mass index (LVMI) were evaluated before and after supplementation.. There was a significant increase in 25(OH)D levels after supplementation (p < 0.001); however, serum calcium (p = 0.02), phosphorus (p = 0.018), and iPTH (p = 0.03) were decreased. Magnesium levels increased during the study (p = 0.03). A reduction in the number of patients under active vitamin D (p < 0.001) and in the dose and number of patients treated with darbepoetin (p = 0.02) was observed. Serum albumin increased (p < 0.001), and C-reactive protein decreased (p = 0.01). BNP (p < 0.001), PP (p = 0.007), and LVMI (p = 0.02) were significantly reduced after supplementation.. Long-term cholecalciferol supplementation allowed correction of 25(OH)D deficiency, improved mineral metabolism with less use of active vitamin D, attenuated inflammation, reduced the dose of the erythropoiesis-stimulating agent, and improved cardiac dysfunction.

Topics: Cholecalciferol; Dietary Supplements; Humans; Inflammation; Minerals; Prospective Studies; Renal Dialysis; Vitamin D; Vitamin D Deficiency; Vitamins

This trial aimed to determine the possible therapeutic and immunomodulatory effects of vitamin D3 in patients with knee OA. In this open-label clinical trial, symptoms were assessed over 3 months in patients with primary knee OA receiving oral vitamin D3 4000 IU/day. Clinical response was evaluated at baseline and 3 months using WOMAC subscores and VAS. Serum levels of cytokines IL-1β, TNF-α, IL-13, IL-17, IL-33, IL-4, and IL-10 were determined by ELISA method. Eighty patients with knee OA were included. All 80 completed the study; the median 25(OH)D3 level was 23.1 ng/ml at baseline and increased by 12.3 ng/ml after treatment. Vitamin D3 after 3 months of supplementation induced a significant reduction in VAS pain and WOMAC subscores. Using OMERACT-OARSI criteria, 86.7% of patients treated with vitamin D3 responded to treatment. At the end of 3 months, systemic values of IL-1β (p < 0.01), IL-23 (p < 0.01), and IL-33 (p < 0.01) were significantly increased, values of TNF-α (p < 0.01), IL-13 (p < 0.01), and IL-17 (p < 0.01) were significantly decreased, while value of IL-4 was not significantly changed. No adverse events were detected. Treatment with vitamin D is associated with improvement in pain, as well as stiffness and physical function. Vitamin D supplementation increased systemic values of IL-33. Our results indicate that vitamin D3 supplementation may be used as a novel therapeutic in knee OA. Future studies are needed to investigate a potential role of IL-33 in the pathogenesis of knee OA.

Topics: Cholecalciferol; Dietary Supplements; Double-Blind Method; Humans; Inflammation; Inflammation Mediators; Interleukin-13; Interleukin-17; Interleukin-33; Osteoarthritis, Knee; Pain; Tumor Necrosis Factor-alpha; Vitamin D

Inflammation is a key factor in the development of ulcerative colitis (UC). 1,25-dihydroxyvitamin D

Topics: Animals; Cholecalciferol; Colitis, Ulcerative; Inflammasomes; Inflammation; Mice; Signal Transduction; Vitamin D

Atopic dermatitis (AD) is a chronic, relapsing, and extremely pruritic inflammatory skin disease with a particular impact on children. AD pathogenesis is not yet fully understood, and there is no curative treatment for this disease. Therefore, several genetically or chemically-induced AD mouse models have been developed. These preclinical mouse models are an indispensable research tool for studying AD pathogenesis and evaluating the efficacy of new candidate AD therapeutics. A commonly used mouse model of AD has been developed using the topical application of a low-calcemic analog of vitamin D3, MC903, to induce AD-like inflammatory phenotypes that closely resemble human AD. Moreover, this model shows a minimal effect on systemic calcium metabolism that is observed in the vitamin D3-induced AD model. Thus, an expanding number of studies use the MC903-induced AD model to interrogate AD pathobiology in vivo and to test new candidate small molecule and monoclonal antibody therapies. This protocol describes in detail functional measurements including the measurement of skin thickness, which is a surrogate marker for ear skin inflammation, as well as itch assessment, histological evaluation to assess the structural changes associated with AD skin inflammation, and preparation of single-cell suspensions from ear skin and draining lymph nodes for the assessment of inflammatory leukocyte subset infiltration in these tissues using flow cytometry. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Topical application of MC903 induces AD-like skin inflammation Support Protocol 1: Measurement of ear skin thickness Support Protocol 2: Itch assessment Support Protocol 3: Dissection of ear skin and ear draining lymph nodes Support Protocol 4: Histological evaluation and quantification Support Protocol 5: Preparation of single-cell suspension from ear skin and draining lymph nodes for the assessment of inflammatory immune cell infiltration using flow cytometry.

Topics: Animals; Child; Cholecalciferol; Cytokines; Dermatitis, Atopic; Humans; Inflammation; Mice; Skin

Atopic dermatitis (AD) is a multifactorial disease with underlying barrier disruption and altered microbial flora, resulting in dry skin and eczematous inflammation with persistent pruritis. Mouse models have been heavily used to investigate AD pathophysiology. Among various AD mouse models, AD-like inflammation induced by topical calcipotriol, a vitamin D3 analog referred to as MC903 in experimental settings, is a versatile model that can be applied to any strain of mice, which can be used for immunologic and morphologic studies. Herein, we provide basic protocols for the topical application of MC903 and approaches to assess phenotypes. After inducing AD-like inflammation, the skin is harvested for flow cytometry analysis, as well as for histologic and immunofluorescence microscopy analyses. The combination of these approaches enables accurate characterization of the degree of inflammation, type of inflammatory infiltrate, and localization of immune infiltrates. Published 2023. This article is a U.S. Government work and is in the public domain in the USA. Basic Protocol 1: Application of MC903 and gross phenotype assessment Basic Protocol 2: Processing skin for flow cytometry analysis Support Protocol: Skin immune cell surface staining and flow cytometry analysis Basic Protocol 3: Harvesting skin for histologic analysis Basic Protocol 4: Immunofluorescence staining to identify immune cell infiltrates.

Topics: Animals; Cholecalciferol; Dermatitis, Atopic; Inflammation; Mice; Phenotype; Skin

Owing to the emergence and spread of multidrug resistance mechanisms in. We established an. Our results demonstrated that. This study indicates the advantage of combining vitamin D3 and probiotic to attenuate

Topics: Anti-Inflammatory Agents; Cholecalciferol; Epithelial Cells; Gastric Mucosa; Helicobacter Infections; Helicobacter pylori; Humans; Inflammation; Levilactobacillus brevis

Vitamin D3 may suppress microglial activation and neuroinflammation, which play a central role in the pathophysiology of many neurological disorders. Sirt6 can remove histone 3 lysine 9 acetylation (H3K9ac) to repress expression of pathological genes and produce anti-inflammatory effects. However, whether vitamin D3 upregulates microglial Sirt6 to exert its protective effects against microglial activation and neuroinflammation is unclear. The effects of lower, normal, and higher dosages (1, 10 and 100 μg/kg/day) of vitamin D3 on behavioral and neuromorphological changes, brain inflammatory factors, Sirt6 and H3K9ac levels, and microglial Sirt6 distribution in hippocampus were evaluated in lipopolysaccharide (LPS)-stimulated mice. In addition, the effects of vitamin D3 on inflammatory factors, reactive oxygen species, Sirt6, and H3K9ac were confirmed in LPS-stimulated BV-2 cells. We verified that vitamin D3 ameliorated the impaired sociability of LPS-stimulated mice by three-chamber test. In addition, vitamin D3 upregulated brain Sirt6 generation, reduced H3K9ac levels and inhibited generation of brain inflammatory factors. Moreover, vitamin D3 promoted microglial Sirt6 distribution and attenuated microglia displaying an activated morphology in the hippocampus of LPS-stimulated mice. Similarly, vitamin D3 upregulated Sirt6 generation and intensity, reduced H3K9ac levels, and inhibited the inflammatory activation of LPS-stimulated BV-2 cells. In conclusion, vitamin D3 may upregulate microglial Sirt6 to reduce H3K9ac and inhibit microglial activation, thereby antagonizing neuroinflammation.

Topics: Animals; Cholecalciferol; Inflammation; Lipopolysaccharides; Mice; Microglia; Neuroinflammatory Diseases; Sirtuins; Up-Regulation

Childhood overweight and obesity have been described by the World Health Organization as noncommunicable diseases and among the greatest public health threats since they have reached epidemic proportions. A child with obesity risks becoming an adult with obesity and developing metabolic and hemostatic disorders which are the basis for the development of coronary heart diseases. Recently, a number of clinical reports have demonstrated that both an increase in plasminogen activator inhibitor-1 (PAI-1) and a deficiency in 25OH-vitamin D3 (VD) are associated with an increase in thrombotic episodes.. PAI-1 and VD levels were measured in 259 clinically overweight and obese children aged between 2 and 18 years enrolled in the Nutritional Education Program of the Bambino Gesù Children's Hospital and Research Institute of Rome (Italy) and 80 normal-weight subjects.. We observed increased HOMA-IR, PAI-1, and other inflammation indices associated with decreased VD levels when compared to normal-weight children.. Our results demonstrated that overweight and obesity are correlated with higher levels of the inflammation index. Moreover, our patients show high PAI-1 and low VD levels, confirming the high thrombotic risk in our pediatric population.

Topics: Adolescent; Adult; Child; Child, Preschool; Cholecalciferol; Humans; Inflammation; Overweight; Pediatric Obesity; Plasminogen Activator Inhibitor 1; Vitamin D; Vitamins

Inflammatory markers play an important role in the pathophysiology of patients with oral problems such as oral lichen planus. This study aimed to investigate the relationship between vitamin D levels and inflammatory markers and total antioxidants in people with oral lichen planus. In this case-control study, 131 patients with oral lichen planus (67 in the lichen planus group and 54 in the control group) were examined. 8 cc of blood was taken from all participants to assess blood factors, inflammatory markers and antioxidant levels. Data were analyzed using SPSS statistical software. The mean age of subjects was 42 years. Vitamin D3 levels in the lichen planus group were lower than in the control group, but this decrease was not statistically significant (P> 0.05). According to statistical findings in the lichen planus group, there was a significant relationship between vitamin D3 levels, inflammatory markers and cellular stress factors (P≤0.05). It is concluded that vitamin D3 in people with oral lichen planus can play an important role in the pathogenesis of oral disease and increase inflammation. Because patients with oral lichen planus are affected by various inflammatory factors, paying attention to vitamin D levels in these patients can be effective in reducing inflammation caused by lichen planus.

Topics: Adult; Antioxidants; Biomarkers; Case-Control Studies; Cholecalciferol; Humans; Inflammation; Lichen Planus; Lichen Planus, Oral; Vitamin D

Chronic iron overload could induce nephropathy via oxidative stress and inflammation, and chelating therapy has limited efficacy in removing excess intracellular iron. Although vitamin D (VD) has shown potent antioxidant and anti-inflammatory effects, as well contribute to iron homeostasis, none of the previous studies measured its potential remedial effects against chronic iron toxicity.. To measure the alleviating effects of deferasirox (DFX) and/or vitamin D (VD) single and combined therapies against nephrotoxicity induced by chronic iron overload.. iron-induced nephrotoxicity was associated with dysregulations in renal VD-system together with renal oxidative stress, inflammation, and apoptosis. While DFX reduced systemic iron, VD monotherapy showed better attenuation of renal iron concentrations and tissue damage. Nonetheless, the co-therapy approach exhibited the maximal remedial effects, possibly by enhanced modulation of renal iron-homeostatic molecules alongside reducing systemic iron levels.. All data generated or analysed during this study are included in this published article [and its Supplementary information files].

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Caspase 3; Cholecalciferol; Deferasirox; Ferritins; Hepcidins; Hydrogen Peroxide; Inflammation; Interleukin-10; Interleukin-6; Iron; Iron Overload; Kidney; Low Density Lipoprotein Receptor-Related Protein-2; Male; Oxidative Stress; Rats; Receptors, Transferrin; Superoxide Dismutase-1; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D3 24-Hydroxylase

Vitamin D is a fat-soluble secosteroid, its primary function being regulation of calcium-phosphate homeostasis and maintenance of bone integrity and mineralization. Recently, pleotropic effects of this vitamin have been recognized, including an immunomodulatory role and involvement in normal brain development and functioning.

Topics: Animals; Bone Density Conservation Agents; Cholecalciferol; Inflammation; Lipopolysaccharides; Rats; Vitamin D; Vitamins

Topics: Animals; Cholecalciferol; Epithelial Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Lung; Mice; Mitochondrial Dynamics; Mitophagy; Pneumonia; Tumor Necrosis Factor-alpha

Vitamin D

Topics: Animals; Antioxidants; Cholecalciferol; Diquat; Gene Expression Regulation; Heme Oxygenase-1; Inflammation; Male; Membrane Proteins; Mice; Mice, Inbred ICR; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Protective Agents; Vitamins

Atherosclerosis (AS) is a cardiovascular disease that arise due to dysfunction of lipid deposition and metabolism. AS is causes the mortality and morbidity worldwide. Sinomenine isolated from the Sinomenium acutum is used extensively against the various cardiac diseases in China. However, the anti-atherosclerosis effect of sinomenine still not explore. In this study, we explore the cardioprotective and anti-atherosclerosis effect of sinomenine against Vitamin D3 and High fat induced atherosclerosis in rats. Sprague Dawley (SD) rats were used in this study. The rats were received the vitamin D (60000) and High fat diet to induce the atherosclerosis and divided into groups and received the oral administration of sinomenine (2.5, 5 and 10 mg/kg) and simvastatin (5 mg/kg). Body weight, organ weight and biochemical parameters were estimated. The mRNA expression of MyD88, TLR4, NF-κB and IκB were estimated. Sinomenine treated rats significantly (p<0.001) suppressed the body weight and modulated the organ weight (hepatic, renal and heart). Sinomenine significantly (p<0.001) decreased the level of triacylglycerols (TG), low density lipoprotein cholesterol (LDL-c), total cholesterol (TC), very low-density lipoprotein cholesterol (VLDL-c) and augmented the level of high-density lipoprotein cholesterol (HDL-c). Sinomenine treatment also reduced the level of atherogenic index (TC/HDL-c and LDL-c/HDL-c). Sinomenine treatment decrease the ratio of HMG CoA/Mevalonate and level of collagen and total protein. Sinomenine significantly (p<0.001) altered the level of heart parameters, antioxidant parameters and inflammatory cytokines. Sinomenine significantly (p<0.001) reduced the expression of MyD88, TLR4, NF-κB and IκB. Taken together, sinomenine exhibited the protective effect against the atherosclerosis via alteration of TLR4/NF-κB signaling pathway.

Topics: Administration, Oral; Animals; Antioxidants; Atherosclerosis; Cholecalciferol; Cytokines; Diet, High-Fat; Inflammation; Inflammation Mediators; Lipid Metabolism; Male; Morphinans; NF-kappa B; Oxidative Stress; Phytotherapy; Rats, Sprague-Dawley; Signal Transduction; Sinomenium; Toll-Like Receptor 4

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Topics: Black People; Cholecalciferol; COVID-19; Hispanic or Latino; Humans; Inflammation; Risk Factors; SARS-CoV-2; United States; Vitamin D Deficiency; Vitamins

The present study explored the possible mitigative effects of vitamin D

Topics: Animals; Antioxidants; Catfishes; Cholecalciferol; Immunity, Innate; Inflammation; Intestines; Lipopolysaccharides; Oxidative Stress; Tight Junctions

Chito-oligosaccharides (CHOS) are oligomers of D-glucosamine and N-acetyl-glucosamine. Anti-inflammatory activities of a wide variety of CHOS mixtures have previously been reported, mainly based on studies with mouse models and murine macrophages. Since the mouse and human immune systems are quite different, gaining insight into the activity of CHOS on human cell lines, using well-characterized CHOS mixtures, is of considerable interest. Bacillus subtilis chitosanase (BsCsn46A) can efficiently convert chitosan to mixtures of water soluble low molecular weight CHOS. Here, the anti-inflammatory activity of a properly characterized CHOS mixture was studied, using human THP-1 cells that were differentiated to mature monocytes using vitamin D3. Addition of CHOS reduced the production of multiple pro-inflammatory cytokines associated with bacterial lipopolyssacharide (LPS)-stimulated inflammation, in a dose-dependent manner and without affecting cell viability. Interestingly, only minimal effects of CHOS were observed in similar experiments with phorbol 12-myristate 13-acetate- (PMA-) differentiated, macrophage-like, THP-1 cells. Altogether, in addition to showing promising biological effects of well-characterized low molecular weight soluble CHOS in a human system, the present study also points at Vitamin D3-stimulated THP-1 cells as a favorable system for assessing the anti-inflammatory activity of bioactive compounds.

Topics: Anti-Inflammatory Agents; Cell Differentiation; Cell Survival; Chitosan; Cholecalciferol; Humans; Inflammation; Oligosaccharides; THP-1 Cells

Lead (Pb) is an environmental toxin that has the ability to alter biological processes by inducing oxidative stress (OS) and inflammation. Nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) are two transcriptional factors that participate in the regulation of cellular responses against OS and inflammation. This study was conducted to evaluate the effects of vitamin D3 (VD) on the prevention of testicular damages of Pb and its association with Nrf2 and NF-κB gene expression levels and their downstream molecules. Forty male Wistar rats were divided into four groups and treatments were performed as following for four weeks: control group received no treatment, VD group were injected intramuscularly with 1000 IU of VD/Kg every other day, Pb group received 1000 mg of Pb/L of drinking water, and Pb + VD group were exposed to Pb and VD simultaneously. The results demonstrated significant decrease in the levels of tissue antioxidants, and increase in inflammatory cytokines in the Pb-intoxicated group, with increased Nrf2 and NF-κB mRNA levels. A remarkable reduction in sperm criteria and a significant disruption in serum hormones were also observed. Anyhow, VD supplementation during exposure to Pb showed a significant protective effect against all pathophysiologic alterations caused by Pb. Furthermore, VD affected the expression of Nrf2 and NF-κB and mitigated the harsh effects of Pb. In conclusion, our findings indicate that VD attenuated the toxic impacts of Pb on testis through modulation of Nrf2 and NF-κB gene expression levels which further regulated the OS and inflammatory responses.

Topics: Animals; Antioxidants; Cholecalciferol; Cytokines; Gene Expression; Hazardous Substances; Inflammation; Lead; Lipid Peroxidation; Male; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Protective Agents; Rats, Wistar; Signal Transduction; Testis

Digital dermatitis (DD), a common ulcerative disease of the bovine foot causing lameness and reducing productivity and animal welfare, is associated with infection by spirochete Treponema bacteria. Topical tetracycline, the most common treatment, has inconsistent cure rates; therefore, new therapeutic options are needed. We compared effects of topical oxytetracycline and vitamin D

Topics: Animals; beta-Defensins; Cattle; Cell Line; Chemotactic Factors; Cholecalciferol; Digital Dermatitis; Epithelial Cells; Humans; Inflammation; Interleukin-8; Oxytetracycline; Skin; Toll-Like Receptor 2; Transcription, Genetic; Treponema

Phospholipases are enzymes that occur in many types of human cells, including mast cells, and play an important role in the molecular background of asthma pathogenesis, and the development of inflammation NF-κB activities that affect numerous biological processes has been reported in many inflammatory diseases including asthma. Vitamin D is a widely studied factor that affects many diseases, including asthma. The aim of this study is to assess the influence of 1,25-(OH)2D3 on regulation of chosen phospholipase-A2 (PLA2) expression-selected inflammation mediators.. LUVA mast cells were stimulated with 1,25(OH)2D3, and inhibitors of NF-κB p65 and ubiquitination. Expression analysis of phospholipases (PLA2G5, PLA2G10, PLA2G12, PLA2G15, PLA2G4A, PLA2G4B, PLA2G4C, PLAA, NF-κB p65, and UBC) was done utilizing real-time PCR and Western blot. Eicosanoid (LTC4, LXA4, 15[S]-HETE, and PGE2) levels and sPLA2 were also measured.. We found that 1,25(OH)2D3 decreased the expression of PLA2G5, PLA2G15, PLA2G5,UBC, and NF-κB p65 but increased expression of PLAA and PLA2G4C (p < 0.05). Moreover, the expression of PLA2G5 and PLA2G15 decreased after inhibition of NF-κB p65 and UBC. Increased levels of released LXA4 and 15(S)-HETE, decreased levels of LTC4, and sPLA2s enzymatic activity in response to 1,25(OH)2D3 were also observed. Additionally, NF-κB p65 inhibition led to an increase in the LXA4 concentration.. Future investigations will be needed to further clarify the role of 1,25(OH)2D3 in the context of asthma and the inflammatory process; however, these results confirm a variety of effects which can be caused by this vitamin. 1,25(OH)2D3-mediated action may result in the development of new therapeutic strategies for asthma treatment.

Topics: Asthma; Cell Line, Transformed; Cholecalciferol; Gene Expression Regulation; Humans; Inflammation; Lipoxins; Mast Cells; NF-kappa B; Phospholipases A2; Signal Transduction; Ubiquitination

Vitamin D

Topics: Animals; Brain; Cholecalciferol; Cholesterol; Disease Models, Animal; gamma-Aminobutyric Acid; Glutamic Acid; Inflammation; Male; Membrane Fusion; Mice, Inbred C57BL; Nervous System Diseases; Neural Pathways; Phospholipids; Rats; Rats, Wistar; Reactive Oxygen Species; Receptors, Metabotropic Glutamate; Synapses; Vitamin D Deficiency; Vitamins

In our previous study, a Seesaw model was proposed for the fluctuation of crucial anti- (IL-10) and pro-inflammatory (Il-6 & IL-17A) cytokines through vitamin D3. In this paper, however, it is intended to extend the mentioned model by assessing the expression mRNA levels of IL-27 and TGF-β1 as well as the changes of plasma levels of IL-27, TGF-β1, IL-17A, IL-10, and IL-6 after treatment by vitamin D3.. Venous blood samples were drawn from Healthy Participants (HP, n = 25) and First-Degree Relative Participants (FDRP, n = 25) as control groups and Multiple Sclerosis Participants (MSP, n = 25) before and after eight weeks of supplementation with 50000 IU vitamin D3. The mRNA expression and plasma concentrations were gauged by using Real-Time PCR and ELISA assay, respectively.. The mRNA surfaces of IL-27, as well as TGF-β1, were up-regulated. However, the plasma levels of TGF-β1, IL-17A, and IL-6 were significantly different among the three groups. In addition, the plasma levels of IL-27, TGF-β1, IL-10, IL-17A, and IL-6 significantly changed following the administration of vitamin D3.. The findings of this paper illustrate that anti-inflammatory cytokines could have a key role in immunomodulatory functions due to their anti-inflammatory functions. To conclude, this might contribute to preventing the pathophysiological process of MS. Also, the proposed model could be used as a preventive way on disposed people to multiple sclerosis, particularly in first degree relatives of these patients.

Topics: Adult; Cholecalciferol; Enzyme-Linked Immunosorbent Assay; Family; Female; Healthy Volunteers; Humans; Inflammation; Interleukins; Male; Multiple Sclerosis; Real-Time Polymerase Chain Reaction; RNA, Messenger; Transforming Growth Factor beta1; Treatment Outcome; Up-Regulation; Young Adult

Topics: Adult; Cells, Cultured; Cholecalciferol; Coinfection; Cytokines; Humans; Inflammation; Leukocytes, Mononuclear; Middle Aged; Pneumococcal Infections; Respiratory Syncytial Virus Infections; Th17 Cells; Toll-Like Receptors; Young Adult

Male Wistar rats were divided into five groups. The passive avoidance test and Morris water maze (MWM) test were conducted to evaluate the learning and memory function. Oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), total thiol content as well as interleukin (IL)-6 were evaluated in the hippocampus tissue.. The intraperitoneal (i.p.) injection of LPS (1 mg/kg) correlates with deficits in passive avoidance and spatial learning in the systemic inflammation model. However, pretreatment with vitamin D. In conclusion, our results suggest that vitamin D

Topics: Animals; Avoidance Learning; Cholecalciferol; Cognitive Dysfunction; Dose-Response Relationship, Drug; Hippocampus; Inflammation; Lipopolysaccharides; Male; Maze Learning; Memory Disorders; Oxidative Stress; Rats; Rats, Wistar

In this report, we designed conjugates of an antigen peptide with the immunosuppressive vitamins all-trans retinoic acid (ATRA) and vitamin D3 for efficient induction of antigen-specific immunotolerance. We established a synthetic scheme for the preparation of the peptide-vitamin conjugates, which the chemically unstable vitamins tolerated. Among the obtained conjugates, the ATRA conjugate successfully suppressed inflammatory effects in macrophages and dendritic cells and induced antigen presentation in dendritic cells. This synthetic method of conjugate is conceivably applicable to other antigen peptides for induction of antigen-specific immunotolerance.

Topics: Animals; Antigen Presentation; Cell Survival; Cells, Cultured; Cholecalciferol; Dendritic Cells; Dose-Response Relationship, Drug; Immune Tolerance; Immunosuppressive Agents; Inflammation; Lipopolysaccharides; Macrophages; Mice; Molecular Structure; Peptides; RAW 264.7 Cells; Tretinoin

Macrophages exert an important role in maintaining and/or ameliorating the inflammatory response. They are involved in the activation of an immune response to pathogens, with a balance between the immunomodulatory role and tissue integrity maintenance, however, excessive macrophage activity promotes tissue injury and chronic disease pathogenesis. There is a high interest in evaluating the anti-inflammatory properties of new botanical preparations. Stimunex® and Stimunex D3® are two food supplements formulated as syrups, containing the extract of elderflower (Sambucus nigra, Caprifoliaceae), standardized in polyphenol (6%) and anthocyanins (4%), associated with wellmune WGP® β-glucan, with the addiction of vitamin D3 (in Stimunex D3® formulation). The aim of the work was the evaluation of Stimunex® and Stimunex D3® activity in human polarized-macrophages, in order to support their use as supplement for preventing and reducing the inflammatory processes. In primary human stimulated macrophages, both syrups were able to revert LPS- and IL-4/IL-13-mediated response, reducing the release of several pro-inflammatory cytokines. Results support that these standardized botanical preparations fortified with β-glucan, may have a potential use in the prevention and coadjuvant management of inflammatory process as respiratory recurrent infections and other similar conditions. Moreover, the addition of vitamin D3 revealed to be an advantage in Stimunex D3® for its important role in maintaining and enhancing the innate immune response.

Topics: Anti-Inflammatory Agents; Cell Line; Cholecalciferol; Cytokines; Humans; Immunity, Innate; Inflammation; Interleukin-13; Interleukin-4; Lipopolysaccharides; Macrophages; Monocytes; Plant Extracts; Sambucus nigra

BACKGROUND Rifaximin is an antimicrobial agent used to treat inflammatory bowel disease (IBD). Vitamin D3 can control IBD due to its effects on inflammatory cytokines. The purpose of this study was to assess the effect of vitamin D3 on the intestinal flora of a dextran sulfate sodium (DSS)-induced mouse model treated with rifaximin. MATERIAL AND METHODS The mouse model of IBD was developed using DSS (4%) administered via the drinking water. Twenty-four male C57BL6 mice were divided into the control group with a normal diet (N=6), the DSS group with a normal diet (N=6), the DSS group with a normal diet treated with rifaximin (N=6), and the DSS group with a normal diet treated with rifaximin and vitamin D3 (N=6). After 14 days, the colonic tissue was studied histologically. Serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1ß (IL-1ß) and enzyme-linked immunosorbent assay (ELISA) were used to measure the level of IL-6 and P65, and phospho-p65 was measured by western blot. 16S rRNA gene sequencing was used to analyze fecal samples. RESULTS In the DSS mouse model of IBD, rifaximin reduced the inflammation severity of the colon and reduced the expression of phospho-p65, p65, TNF-alpha, and IL-6. In the DSS+rifaximin+vitamin D3 group, the therapeutic influences of rifaximin, in terms of weight loss and colonic disease activity, were significantly reduced, and the gut microbiota of the mice were completely changed in composition and diversity. CONCLUSIONS In a mouse model of IBD, treatment with vitamin D3 significantly increased the metabolism of rifaximin and reduced its therapeutic effects.

Topics: Animals; Cholecalciferol; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Gastrointestinal Microbiome; Inflammation; Inflammatory Bowel Diseases; Male; Mice, Inbred C57BL; Phylogeny; Rifaximin

Topics: Allergens; Animals; Asthma; Bronchoalveolar Lavage Fluid; Cholecalciferol; Cytokines; Desensitization, Immunologic; Disease Models, Animal; Eosinophils; Female; Hypersensitivity; Immunoglobulin E; Immunoglobulin G; Inflammation; Lung; Mice; Mice, Inbred BALB C; Poaceae; Pollen; Respiratory Hypersensitivity

Several epidemiological reports demonstrated that vitamin D deficiency elevated risk of preterm delivery. We investigate the effects of oral cholecalciferol (VD3) supplementation on lipopolysaccharide (LPS)-induced preterm delivery. Pregnant mice were randomly assigned to either oral VD3 (25 μg/kg) or corn oil once daily from gestational day (GD)13 to GD15, and were intraperitoneally injected with either LPS (200 μg/kg) or normal saline on GD15. As expected, LPS was effective in inducing preterm delivery and fetal death. LPS-induced preterm delivery and fetal death were alleviated in VD3-pretreated mice. LPS-induced down-regulation of genes for placental progesterone biosynthetic enzymes was blocked in VD3-pretreated mice. LPS-induced reduction of serum progesterone was correspondingly attenuated by VD3. Although oral VD3 had no effect on estradiol production, it attenuated LPS-induced up-regulation of placental ERβ in mice. LPS-induced placental COX-2 up-regulation and serum PGF2α elevation were alleviated in VD3-pretreated mice. Additionally, LPS-evoked elevations of the placental Tnfα, Il1β, Mcp1 and Mip2 mRNAs were attenuated by VD3. VD3 promoted placental vitamin D receptor nuclear translocation and simultaneously alleviated LPS-induced nuclear translocation of NF-κB p65 and p50 subunits. These results provide evidence that oral VD3 supplementation alleviates LPS-induced preterm delivery and fetal demise partially through regulating placental steroid hormones and prostaglandins.

Topics: Administration, Oral; Animals; Cholecalciferol; Dietary Supplements; Estradiol; Female; Humans; Inflammation; Lipopolysaccharides; Mice; Mice, Inbred ICR; Placenta; Pregnancy; Premature Birth; Progesterone; Prostaglandins; Receptors, Calcitriol

The probably effects of sitagliptin and vitamin D3 (VitD3) on proliferation capacity and cytokines production were investigated in type 2 diabetes mellitus (T2DM) in vitro.. Peripheral blood mononuclear cells (PBMCs) were isolated from 35 patients with T2DM and 26 healthy controls (HCs). CFSE-labeled PBMCs stimulated with phytohamagglutinin (PHA, 5 μg/mL) in the presence/absence of sitagliptin (200 mg/mL) with/without VitD3 (10. The proliferation of CD4. Sitagliptin plus VitD3 effectively reduces the proliferative T cells response and modulates pro-inflammatory/anti-inflammatory cytokines production.

Topics: Adult; Cell Proliferation; Cells, Cultured; Cholecalciferol; Cytokines; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Inflammation; Male; Middle Aged; Sitagliptin Phosphate; T-Lymphocytes; Vitamins

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intracellular neurofibrillary tangles and extracellular Aβ deposition. Growing experimental evidence indicate diverse biological effects of vitamin D

Topics: Alzheimer Disease; Animals; Antioxidants; Behavior, Animal; Cholecalciferol; Cognition; Cognition Disorders; Disease Models, Animal; Hippocampus; Inflammation; Male; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Streptozocin

Poor corneal permeability, nasolacrimal drainage and requirement of chronic administration are major drawbacks of existing therapies for ocular inflammation. Hence, we designed topical micelles of PEG. Integrin targeted tacrolimus loaded PEGCCF micelles (TTM) were prepared by solvent diffusion evaporation method and characterized for particle size, osmolality, encapsulation efficiency and drug loading. Therapeutic potential of TTM was evaluated in benzalkonium chloride induced ocular inflammation model in BALB/c mice. Corneal flourescein staining and histopathological analysis of corneal sections was performed.. TTM had a particle size of 45.3 ± 5.3 nm, encapsulation efficiency (88.7 ± 0.9%w/w) and osmolality of 292-296 mOsmol/Kg. TTM significantly reduced the corneal fluorescence as compared to tacrolimus suspension (TACS). H&E staining showed that TTM could restore corneal epithelial thickness, reduce stromal edema (p < 0.05) and decrease number of inflammatory cells (p < 0.01) compared with TACS. Immunohistochemistry analysis demonstrated lower expression of Ki67 + ve cells (p < 0.05) and IL-6 throughout the cornea against TACS (p < 0.01) and the control (p < 0.001).. TTM is an innovative delivery system for improving ocular inflammation due to a) integrin targeting b) PEGCCF in the form of carrier and c) anti-inflammatory and synergistic effect (due to Pgp inhibition) with TAC.

Topics: Administration, Ophthalmic; Animals; Benzalkonium Compounds; Cholecalciferol; Disease Models, Animal; Drug Carriers; Drug Compounding; Eye; Eye Diseases; Female; Humans; Inflammation; Integrins; Mice; Mice, Inbred BALB C; Micelles; Polyethylene Glycols; Tacrolimus

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have been shown to be vitamin D3 (VD3) deficient, which is associated with more severe disease and increased polyp size. To gain mechanistic insights into these observational studies, we examined the impact of VD3 deficiency on inflammation and VD3 metabolism in an Aspergillus fumigatus (Af) mouse model of chronic rhinosinusitis (Af-CRS).. Balb/c mice were fed control or VD3 deficient diet for 4 weeks. Mice were then sensitized with intraperitoneal Af, and one week later given Af intranasally every three days for four weeks while being maintained on control or VD3 deficient diet. Airway function, sinonasal immune cell infiltrate and sinonasal VD3 metabolism profiles were then examined.. Mice with VD3 deficiency had increased Penh and sRaw values as compared to controls as well as exacerbated changes in sRaw when coupled with Af-CRS. As compared to controls, VD3 deficient and Af-CRS mice had reduced sinonasal 1α-hydroxylase and the active VD3 metabolite, 1,25(OH)2D3. Differential analysis of nasal lavage samples showed that VD3 deficiency alone and in combination with Af-CRS profoundly upregulated eosinophil, neutrophil and lymphocyte numbers. VD3 deficiency exacerbated increases in monocyte-derived dendritic cell (DC) associated with Af-CRS. Conversely, T-regulatory cells were decreased in both Af-CRS mice and VD3 deficient mice, though coupling VD3 deficiency with Af-CRS did not exacerbate CD4 or T-regulatory cells numbers. Lastly, VD3 deficiency had a modifying or exacerbating impact on nasal lavage levels of IFN-γ, IL-6, IL-10 and TNF-α, but had no impact on IL-17A.. VD3 deficiency causes changes in sinonasal immunity, which in many ways mirrors the changes observed in Af-CRS mice, while selectively exacerbating inflammation. Furthermore, both VD3 deficiency and Af-CRS were associated with altered sinonasal VD3 metabolism causing reductions in local levels of the active VD3 metabolite, 1,25(OH)2D3, even with adequate circulating levels.

Topics: Animals; Aspergillus fumigatus; Blood Cell Count; Cholecalciferol; Diet; Dietary Supplements; Disease Models, Animal; Eosinophils; Humans; Inflammation; Lymphocytes; Mice; Nasal Lavage; Nasal Polyps; Neutrophils; Rhinitis; Sinusitis; T-Lymphocytes, Regulatory; Vitamin D Deficiency

Exclusive enteral nutrition (EEN) therapy using a polymeric formula (PF) can substantially attenuate intestinal inflammation in Crohn's disease (CD) patients. However, the mechanism(s) by which EEN suppresses inflammation are not yet fully understood. The aims were to examine cellular mechanism(s) through which EEN may suppress inflammation and investigate potential pathways to enhance anti-inflammatory properties of EEN.. Glutamine, arginine, vitamin D. Cellular viability and activity were maintained with all nutrient treatments. Glutamine, arginine, and vitamin D. These data indicate that glutamine, arginine, and vitamin D

Topics: alpha-Linolenic Acid; Anti-Inflammatory Agents; Arginine; Cell Survival; Cholecalciferol; Crohn Disease; Enteral Nutrition; Glutamine; HT29 Cells; Humans; Inflammation; Interleukin-8; NF-kappa B; Nitric Oxide; p38 Mitogen-Activated Protein Kinases; Pharmaceutical Solutions; Phosphorylation; Tumor Necrosis Factor-alpha

Increasing evidence demonstrates that inflammatory cytokines are involved in LPS-induced adverse pregnant outcomes including early embryo loss. Vitamin D3 (VitD3) has anti-inflammatory activity. We aimed to investigate the effects of vitamin D3 (VitD3) on LPS-induced early embryo loss in mice.. All pregnant mice except controls were intraperitoneally (ip) injected with LPS on GD7. In VitD3 alone and LPS+VitD3 groups, pregnant mice were pretreated with VitD3 by gavage daily from GD5 to GD7.. LPS caused 62.5% pregnant mice with early embryo loss. Interestingly, the rate of abortion dropped to 14.3% when pregnant mice were pretreated with VitD3. Additional experiment showed that VitD3 significantly attenuated LPS-evoked elevation on TNF-α, IFN-γ, MIP-2, and nitrate plus nitrite in maternal serum. In addition, VitD3 alleviated LPS-induced COX-2 expression in the decidua and attenuated the elevation of PGF2α in maternal serum. Although VitD3 had no effect on IL-10 in maternal serum, it induced further elevation of serum IL-10 level in LPS-treated mice. Further analysis showed that VitD3 activated VDR signaling, simultaneously inhibited LPS-induced nuclear translocation of NF-κB p65 subunits in the decidua.. VitD3 protects mice from LPS-induced early embryo loss at least partially through its anti-inflammatory effects.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Cholecalciferol; Cyclooxygenase 2; Cytokines; Decidua; Dinoprost; Embryo Loss; Female; Humans; Inflammation; Inflammation Mediators; Lipopolysaccharides; Mice; Mice, Inbred ICR; NF-kappa B; Pregnancy

Erlotinib is a targeted agent commonly used in advanced non-small cell lung cancer (aNSCLC). However, drug-related skin toxicity often may affect the quality of life of cancer patients and lead to treatment discontinuation. Genetic polymorphisms in drug transporters and metabolizing enzymes play a major role in the interindividual variability in terms of efficacy and toxicity of erlotinib treatment. The aim of our study was to identify genetic determinants in adsorption, distribution, metabolism, and excretion genes influencing skin rash (SR) by the novel drug-metabolizing enzyme and transporter (DMET) microarray Affymetrix platform in aNSCLC patients.. In a retrospective study, 34 erlotinib-treated aNSCLC patients were genotyped by DMET Plus chip: 23 patients experienced SR (cases), while 11 patients did not (controls). Peripheral blood DNA was genotyped. Genotype association was analyzed by Fisher's exact test, and the toxicity-associated gene sets underwent Ingenuity Pathway Analysis (IPA).. Seven SNPs in six genes (CYP27B1, MAT1A1, CHST1, CYP4B1, ADH6, and SLC22A1) were associated with the occurrence of SR or with a protective effect. Specifically, the rs8176345 in CYP27B1 gene was significantly correlated with SR (p = 0.0003, OR 55.55, 95% CI 2.7036-1141.1707). The IPA on SR-related genes highlighted the role of a variety of canonical pathways including 1,25-dihydroxyvitamin D3 biosynthesis, S-adenosyl-L-methionine biosynthesis, and methionine degradation I (to homocysteine) in SR development.. Although exploratory, this study indicates rs8176345 in CYP27B1 gene as significantly correlated with erlotinib-induced SR in aNSCLC patients probably through a mechanism mediated by vitamin D3 and inflammation at skin level.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cholecalciferol; Drug Eruptions; Erlotinib Hydrochloride; Female; Genotype; Humans; Inflammation; Lung Neoplasms; Male; Middle Aged; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Quality of Life; Retrospective Studies

Inhibition of pro-inflammatory functions of microglia has been considered a promising strategy to prevent pathogenic events in the central nervous system under neurodegenerative conditions. Here we examined potential inhibitory effects of nuclear receptor ligands on lipopolysaccharide (LPS)-induced inflammatory responses in microglial BV-2 cells. We demonstrate that a vitamin D receptor agonist 1,25-dihydroxyvitamin D

Topics: Animals; Cell Line; Cholecalciferol; Cytokines; Extracellular Signal-Regulated MAP Kinases; Inflammation; Lipopolysaccharides; Microglia; Nitric Oxide; Nitric Oxide Synthase Type II; Phosphorylation; Signal Transduction

Antimicrobial peptides (AMPs) constitute an indispensable arm of innate immunity against infectious microbes in humans. Induction of endogenous AMPs may become an alternative therapy against infections. Our previous studies have demonstrated phenylbutyrate (PBA) as a novel inducer of the AMPs cathelicidin (encoded by the CAMP gene) and human beta-defensin-1 in the human bronchial epithelial cell line VA10. In this work, we have continued by studying molecular mechanisms of PBA mediated induction of LL-37 expression and associated pathways in the human bronchial epithelial cell line VA10. In this study we demonstrate vitamin D receptor (VDR) as a key transcription factor required for PBA mediated up-regulation of the CAMP gene expression. PBA also increases mRNA expression of the vitamin D3 regulated genes CYP24A1 and CD14. The siRNA knockdown of VDR reduced PBA mediated increase in CAMP, CYP24A1 and CD14 expression. Furthermore, we demonstrate that PBA enhances Toll-Like Receptor 5 ligand flagellin regulated mRNA expression of the inflammatory cytokine TNFα and chemokine CXCL8. PBA also up-regulates the expression of the genes encoding the growth factor cytokines transforming growth factor (TGF) α, TGFβ1 and TGFβ2. Our results indicate that TGFβ type I receptor and epidermal growth factor receptor are involved in PBA mediated CAMP regulation. Finally, we show that co-treatment with PBA and vitamin D3 reduces Pseudomonas aeruginosa growth in vitro.

Topics: Antimicrobial Cationic Peptides; beta-Defensins; Cathelicidins; Cell Line; Cholecalciferol; Cytokines; Flagellin; Gene Silencing; Humans; Inflammation; Intercellular Signaling Peptides and Proteins; Ligands; Microbial Sensitivity Tests; Phenylbutyrates; Pseudomonas aeruginosa; Receptors, Calcitriol; RNA, Messenger; Signal Transduction; Toll-Like Receptor 5; Up-Regulation; Vitamin D3 24-Hydroxylase

Vitamin D is associated with skeletal muscle physiology and function and may play a role in intramuscular inflammation, possibly via the vitamin D receptor (VDR). We conducted two studies to examine (1) whether serum 25-hydroxyvitamin D (25OHD) and/or intramuscular VDR protein concentrations are associated with intramuscular interleukin-6 (IL-6) and/or tumor necrosis factor-α (TNFα); and (2) whether 16-week supplementation with vitamin D3 alters intramuscular IL-6 and/or TNFα. Potential-related signaling pathways were also examined. Muscle biopsies of 30 older, mobility-limited adults were obtained at baseline. A subset of 12 women were supplemented with either 4,000 IU/day of vitamin D3 (N = 5) or placebo (N = 7), and biopsies were repeated at 16 weeks. Serum 25OHD was measured, and intramuscular VDR, IL-6, and TNFα gene expressions and protein concentrations were analyzed. Baseline serum 25OHD was not associated with intramuscular IL-6 or TNFα gene expression or protein concentration. Baseline intramuscular VDR protein concentration, adjusted for baseline serum 25OHD, was positively associated with intramuscular IL-6 gene expression (n = 28; p = 0.04), but negatively associated with intramuscular IL-6 protein (n = 18; p = 0.03). Neither intramuscular IL-6 nor TNFα gene expression was different between placebo (n = 7) or vitamin D3 supplementation groups (n = 5) after 16 weeks (p = 0.57, p = 0.11, respectively). These data suggest that VDR is a better predictor than serum 25OHD concentration of intramuscular IL-6 gene and protein expressions. A similar relationship was not observed for TNFα expression. Further, supplementation with 4,000 IU vitamin D3 per day does not appear to affect intramuscular IL-6 or TNFα gene expression after 16 weeks.

Topics: Aged; Aged, 80 and over; Cholecalciferol; Female; Gene Expression; Humans; Inflammation; Interleukin-6; Male; Muscle, Skeletal; Receptors, Calcitriol; Tumor Necrosis Factor-alpha; Vitamin D

Vitamin D level is linked to susceptibility to infections, but its relevance in candidemia is unknown. We aimed to investigate the in vivo sequelae of vitamin D3 supplementation in systemic Candida infection. Implicating the role of vitamin D in Candida infections, we showed that candidemic patients had significantly lower 25-OHD concentrations. Candida-infected mice treated with low-dose 1,25(OH)2D3 had reduced fungal burden and better survival relative to untreated mice. Conversely, higher 1,25(OH)2D3 doses led to poor outcomes. Mechanistically, low-dose 1,25(OH)2D3 induced proinflammatory immune responses. This was mediated through suppression of SOCS3 and induction of vitamin D receptor binding with the vitamin D-response elements in the promoter of the gene encoding interferon γ. These beneficial effects were negated with higher vitamin D3 doses. While the antiinflammatory effects of vitamin D3 are well described, we found that, conversely, lower doses conferred proinflammatory benefits in Candida infection. Our study highlights caution against extreme deviations of vitamin D levels during infections.

Topics: Animals; Candidiasis; Cholecalciferol; Cohort Studies; Dose-Response Relationship, Drug; Gene Expression Regulation; Humans; Inflammation; Interferon-gamma; Leukocytes, Mononuclear; Mice; Mice, Inbred BALB C; Promoter Regions, Genetic; RNA, Messenger; STAT Transcription Factors; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Vitamin D

Vitamin D (VD) displays immunoregulatory effects and reduces adipocyte inflammation, which may participate to a reduction of adipose tissue macrophage infiltration in the context of obesity-associated low-grade inflammation. These observations have been described mainly in vitro, through the evaluation of a limited number of inflammatory markers. Here, we studied the effects of 1,25 dihydroxy-VD on chemokine network expression in adipocytes (by transcriptomic approach), and we confirm the physiological relevance of these data in vivo, by demonstrating the effect of VD on cytokine and chemokine gene expression as well as on macrophage infiltration in adipose tissue. 1,25 dihydroxy-VD down-regulated (-1.3- to -10.8-fold) the mRNA expression of 29 chemokines and limited macrophage migration in TNFα-conditioned adipocyte medium (1.5-fold; P < .05). This effect was associated with a reduction in p65 and IκB (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha) phosphorylation (2-fold compared with TNFα; P < .05). The effects of VD were confirmed in mice injected ip with lipopolysaccharide (acute inflammation) and diet-induced obese mice (metabolic inflammation), where the levels of mRNA encoding proinflammatory cytokines and chemokines (∼2-fold) were reduced in adipocytes (acute and metabolic inflammation) and adipose tissue and that macrophage infiltration was also inhibited in the adipose tissue of obese mice (metabolic inflammation). Altogether, these results showed that VD displayed a global immunoregulatory impact on adipocytes, notably via the inhibition of chemokine expression and macrophage infiltration in inflamed adipose tissue.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Cell Line; Cell Migration Assays, Macrophage; Cell Movement; Chemokines; Cholecalciferol; Cytokines; Gene Expression; Humans; In Vitro Techniques; Inflammation; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred C57BL; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Necrosis Factor-alpha; Vitamin D

We investigated the effects of 4-17 month supplementation with ω-3 fatty acids and antioxidants (Smartfish drink; Smartfish AS, Oslo, Norway) in 12 patients with minor cognitive impairment (MCI) [minimental state examination (MMSE) ≥19], 2 patients with pre-MCI (normal MMSE), and 7 patients with Alzheimer disease (AD) (MMSE <19). We measured the phagocytosis of amyloid-β 1-42 (Aβ) by flow cytometry and microscopy, the transcription of inflammatory genes by RT-PCR, the production of resolvin D1 (RvD1) by enzyme immunoassay, and the cognitive status by MMSE. In patients with MCI and pre-MCI, phagocytosis of Aβ by monocytes increased from 530 to 1306 mean fluorescence intensity units (P = 0.016). The increase in patients with AD was not significant (N.S.). The lipidic mediator RvD1, which stimulates Aβ phagocytosis in vitro, increased in macrophages in 80% of patients with MCI and pre-MCI (mean increase 9.95 pg/ml) (N.S.). Transcription of inflammatory genes' mRNAs was increased in a subgroup of patients with low transcription at baseline, whereas it was not significantly changed in patients with high transcription at baseline. The mean MMSE score of patients with MCI and pre-MCI was 25.9 at baseline and 25.7 after 4-17 months (N.S.). Our study is the first to show significant immune and biochemical effects of ω-3 fatty acids with antioxidants in patients with MCI. Cognitive benefits of ω-3 supplementation in patients with MCI should be tested in a clinical trial.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Cholecalciferol; Cognitive Dysfunction; Dietary Supplements; Docosahexaenoic Acids; Fatty Acids, Omega-3; Female; Humans; Inflammation; Macrophages; Male; Mental Status Schedule; Middle Aged; Monocytes; Phagocytosis; Resveratrol; RNA, Messenger; Stilbenes

Previously, we demonstrated that glucocorticoid (GC) treatment of asthmatic patients resulted in decreasing frequencies of monocyte subsets expressing CD16 and capable of releasing TNF-α. Here, we wished to analyze whether the active form of vitamin D, i.e. vitamin D3, referred to as 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] can exert GC-like proapoptotic effects on CD16-positive monocytes and thus decrease the proinflammatory potential of these cells. Finally, we set out to investigate whether the addition of 1,25-(OH)2D3 would facilitate the use of lower doses of GC without decreasing their anti-inflammatory properties.. Peripheral blood mononuclear cells collected from healthy individuals and asthmatic patients were cultured with 1,25-(OH)2D3 and/or varying doses of GC in the presence or absence of caspase inhibition. The cells were either directly stained for extracellular markers or prestimulated with lipopolysaccharide for the assessment of intracellular cytokine production and then analyzed by flow cytometry.. We found that 1,25-(OH)2D3 alone (and in combination with GC) decreased the frequency of CD14++CD16+ and CD14+CD16++ monocytes from asthmatic patients and significantly diminished TNF-α production by the monocytes. With regard to the CD14+CD16++ subset, the monocyte-depleting effects of 1,25-(OH)2D3 were abrogated in the presence of pan-caspase inhibitor, suggesting a proapoptotic mechanism of 1,25-(OH)2D3 action. Interestingly, we found that a combined treatment of 1,25-(OH)2D3 and GC allowed for a 5-fold reduction of the GC dose while maintaining their anti-inflammatory effects.. This study has revealed novel immunomodulatory properties of 1,25-(OH)2D3 directed against monocyte subsets capable of TNF-α production. In addition, our data suggest that the introduction of 1,25-(OH)2D3 to anti-inflammatory therapy would possibly allow for the use of lower doses of GC.

Topics: Adult; Anti-Inflammatory Agents; Asthma; Caspase Inhibitors; Cholecalciferol; Female; Glucocorticoids; GPI-Linked Proteins; Humans; Inflammation; Lipopolysaccharide Receptors; Male; Monocytes; Receptors, IgG; Tumor Necrosis Factor-alpha

It is increasingly recognized that vitamin D3 (VitD3) has an anti-inflammatory activity. The present study investigated the effects of maternal VitD3 supplementation during pregnancy on LPS-induced placental inflammation and fetal intrauterine growth restriction (IUGR). All pregnant mice except controls were intraperitoneally injected with LPS (100 μg/kg) daily from gestational day (GD)15-17. In VitD3 + LPS group, pregnant mice were orally administered with VitD3 (25 μg/kg) before LPS injection. As expected, maternal LPS exposure caused placental inflammation and fetal IUGR. Interestingly, pretreatment with VitD3 repressed placental inflammation and protected against LPS-induced fetal IUGR. Further analysis showed that pretreatment with VitD3, which activated placental vitamin D receptor (VDR) signaling, specifically suppressed LPS-induced activation of nuclear factor kappa B (NF-κB) and significantly blocked nuclear translocation of NF-κB p65 subunit in trophoblast gaint cells of the labyrinth layer. Conversely, LPS, which activated placental NF-κB signaling, suppressed placental VDR activation and its target gene expression. Moreover, VitD3 reinforced physical interaction between placental VDR and NF-κB p65 subunit. The further study demonstrates that VitD3 inhibits placental NF-κB signaling in VDR-dependent manner. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity. Overall, the present study provides evidence for roles of VDR as a key regulator of placental inflammation.

Topics: Animals; Cholecalciferol; Female; Fetal Growth Retardation; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; Placenta; Placenta Diseases; Pregnancy; Receptors, Calcitriol; Signal Transduction; Transcription Factor RelA

The present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.

Topics: Animals; Anti-Inflammatory Agents; Carps; Cells, Cultured; Cholecalciferol; Dietary Supplements; Down-Regulation; Enterocytes; Fish Diseases; Inflammation; Interleukin-6; Interleukin-8; Intestines; Lipopolysaccharides; RNA, Messenger; Signal Transduction; Toll-Like Receptor 4; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Vitamin D

Aging is associated with a decline in stem cell proliferation that is thought to be a result of dysregulated signaling in the neurogenic niche. This results in a diminished and less efficient pool of progenitors. The Wnt pathway plays a key role in the proliferation and differentiation of progenitor cells. Recent publications suggest that the age-related decline in the function of Wnt is a contributor to age-dependent decline in neural progenitors. Similarly, the aged neurogenic niche is characterized by higher levels of inflammatory cytokines. This increased inflammation contributes to the declining function of neural progenitor cells. NT-020, a proprietary blend of polyphenols, has been shown to increase proliferation of neural progenitors and improve cognitive function in aged rats.. In this study, we examined the neurogenic niche in the subgranular zone of the dentate gyrus (SGZ) and the subventricular zone (SVZ) of young and aged rats to determine if dietary supplementation with NT-020 could regulate inflammation and oxidative stress response pathways in neurons, astrocytes, and microglia. Further, we examined NT-020's ability to modulate Wnt signaling in the aged neurogenic niche. To accomplish this, we utilized gene PCR arrays and immunohistochemistry.. We observed an increase in nuclear localization of immunopositive labeling of β-catenin, HO-1, and Nrf2 in all subsets of cell types in both young and aged rats in the SGZ and SVZ following NT-020 treatment. NeuN-positive cells showed a basal increase in nuclear β-catenin in the aged rats, which was not observed in doublecortin (DCX)-labeled cells, microglia, or astrocytes. Reverse transcription polymerase chain reaction (RT-PCR) analysis of isolated hippocampal tissue revealed that a significant percent of genes involved with inflammation are affected by treatment with NT-020. In addition, several genes that regulate Wnt activity were affected by supplementation.. The results suggest that NT-020 activates oxidative stress response pathways and supports pro-neurogenic gene expression in the hippocampus. This may represent the mechanism by which the NT-020 formula enhances performance in learning and memory tasks in aged mice.

Topics: Aging; Animals; beta Catenin; Calcium-Binding Proteins; Carnosine; Cell Proliferation; Cholecalciferol; Computational Biology; Cytokines; Dentate Gyrus; Doublecortin Domain Proteins; Doublecortin Protein; Inflammation; Intercellular Signaling Peptides and Proteins; Male; Microfilament Proteins; Microtubule-Associated Proteins; Nerve Tissue Proteins; Neurogenesis; Neuropeptides; NF-E2-Related Factor 2; Plant Extracts; Rats; Rats, Inbred F344; Wnt Signaling Pathway

Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury.

Topics: Acute Kidney Injury; Animals; Cell Line; Chemokines; Cholecalciferol; Cyclooxygenase 2; Humans; Inflammation; Intercellular Adhesion Molecule-1; Kidney; Lipopolysaccharides; Male; Mice; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Protein Binding; Proto-Oncogene Proteins c-akt; Receptors, Calcitriol; RNA, Small Interfering; Signal Transduction; Transcription Factor RelA; Transfection; Vascular Cell Adhesion Molecule-1

Alloiococcus otitidis is usually detected in children with otitis media (OM) by PCR as it is not often detected by routine culture. Our improved method for its isolation obtained A. otitidis from nearly 50% of 78 children with OM with effusion. The role of A. otitidis in pathogenesis of OM is unclear. This study tested two hypothesis: (1) that fresh isolates of A. otitidis would elicit pro-inflammatory cytokines from THP-1 monocytic cells equivalent to those induced by Streptococcus pneumoniae; (2) priming THP-1 cells with interferon-gamma (IFN-γ) a surrogate for virus infection, would enhance pro-inflammatory responses. Recent clinical isolates of A. otitidis, S. pneumoniae (ATCC 49619) and a blood culture isolate of S. pneumoniae (SP2) were used in the assays. Cytokines were quantified by BioRad bead assay and Luminex 200. IFN-γ priming enhanced cytokine responses. S. pneumoniae ATCC 49619 induced lower responses than SP2 for IL-1β, IL-6, TNF-α. A. otitidis LW 27 elicited higher IL-1β and TNF-α responses than either pneumococcal isolate. Small green colony types of A. otitidis induced higher responses than large white colony types for IL-8 and IL-1β. The hypothesis that A. otitidis elicits cytokines observed in middle ear effusions was supported; the need to use recent clinical isolates in studies of pathogenesis was highlighted.

Topics: Carnobacteriaceae; Cell Line; Cell Survival; Child; Cholecalciferol; Cytokines; Disinfectants; Formaldehyde; Humans; Inflammation; Interferon-gamma; Mycoplasma; Otitis Media with Effusion; Streptococcal Infections; Streptococcus pneumoniae; Vitamins

Interactions among major risk factors associated with bacterial infections were assessed in a model system using surrogates for virus infection; IFN-g, and exposure to cigarette smoke; cigarette smoke extract (CSE), nicotine and cotinine. Cytokine responses elicited by LPS from THP-1 cells in the presence of these components, or combinations of components, were assessed by multiplex bead assay, i.e. IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-γ. IFN-γ-priming significantly increased pro-inflammatory cytokines induced by LPS. CSE suppressed production of pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ, but enhanced production of IL-8. Nicotine and cotinine suppressed all cytokine responses. In combination, IFN-γ masked the inhibitory effects of CSE. In relation to the objectives of the study, we concluded that (a) IFN-γ at biologically relevant concentrations significantly enhanced pro-inflammatory responses; (b) CSE, nicotine and cotinine dysregulated the inflammatory response and that the effects of CSE were different from those of the individual components, nicotine and cotinine; (c) when both IFN-γ and CSE were present, IFN-γ masked the effect of CSE. There is a need for clinical investigations on the increase in IL-8 responses in relation to exposure to cigarette smoke and increased pro-inflammatory responses in relation to recent viral infection.

Topics: Antigens, Bacterial; Cells, Cultured; Cholecalciferol; Cotinine; Cytokines; Humans; Inflammation; Interferon-gamma; Lipopolysaccharides; Nicotiana; Nicotine; Nicotinic Agonists; Smoke; Tobacco Products; Virus Diseases; Vitamins

Postprandial inflammation is considered to be pro-atherogenic. Vitamin D can reduce inflammation and arterial stiffness. We hypothesized that vitamin D3 improves postprandial arterial elasticity by the modulation of leukocyte activation. Healthy volunteers underwent two oral fat-loading tests (OFLTs). The augmentation index (AIx) and flow cytometric quantification of leukocyte activation markers were measured. After the first OFLT, 100 000 IU of vitamin D3 was administered and a second OFLT was carried out 7 days later. Six men and six women were included. A favorable reduction in AIx was found after vitamin D3 supplementation (P=0.042) in both genders. After vitamin D3, exclusively in women a reduction in the area under the postprandial curve for monocytes CD11b and CD35 by 10.5% (P=0.016) and 12.5% (P=0.04) and neutrophil CD11b by 17.0% (P=0.014) was observed. In conclusion, vitamin D3 probably increased postprandial arterial elasticity in men and women, but reduced postprandial leukocyte activation exclusively in women.

Topics: Adolescent; Adult; Area Under Curve; Biomarkers; CD11b Antigen; CD36 Antigens; Cholecalciferol; Cross-Over Studies; Dietary Supplements; Dose-Response Relationship, Drug; Female; Humans; Inflammation; Leukocytes; Male; Middle Aged; Postprandial Period; Receptors, Complement 3b; Vascular Stiffness; Young Adult

The aim of this study was to examine the effects of cholecalciferol on systemic inflammation and memory in the setting of fatty liver disease in rats.. To induce the development of fatty liver disease, the rats were fed a 35% fructose solution over 8 weeks. Group I (n=6) was designated as the control group and fed with standard rat chow. Group II (n=6) was provided with, standard rat chow, and 0.3 μg/kg/day of oral cholecalciferol over a duration of 2 weeks. In addition to standard rat chow, group III (n=6) and group IV (n=6) were given 4 mL of the 35% fructose solution per day via oral gavage for 8 weeks. However, group IV was also given 0.3 μg/kg/day of oral cholecalciferol over 2 weeks. After the treatment period, passive avoidance tasks were performed by all groups. The liver and brain were harvested for subsequent biochemical and histopathologic analyses.. The development of fatty liver extends the memory latency period of passively avoiding tasks after 1 trial. Moreover, there were increases in brain TNF-α and plasma MDA levels according to two-way analysis of variance. Cholecalciferol supplementation decreased the latency period of passively avoiding tasks in rats with hepatosteatosis, and also significantly reduced brain TNF-α and plasma MDA levels.. Fatty liver may contribute to the development of systemic inflammation, which affects cognition and causes deficits in memory; however, the anti-inflammatory and antioxidant properties of vitamin D may improve the cognitive function of rats with hepatosteatosis.

Topics: Administration, Oral; Animals; Avoidance Learning; Cholecalciferol; Cognition Disorders; Disease Models, Animal; Fatty Liver; Inflammation; Inflammation Mediators; Male; Metabolic Syndrome; Rats; Rats, Sprague-Dawley

Recent experimental data seem to suggest a relevant role for 1,25[OH]2cholecalciferol (1,25[OH]2D3) in adipocyte physiology and pathophysiology, with some studies showing adipogenic and pro-inflammatory properties, and others lipolytic and anti-inflammatory functions. Moreover, to our knowledge, the role of cholecalciferol (D3) in adipocytes function is still not known. Therefore, the aim of this study was to investigate in vitro the effects of 1,25[OH]2D3, as well as of D3, in 3T3-L1 adipocytes in basal and inflammatory conditions, testing the effects of different calcium concentrations in adipocytes culture medium. In 3T3-L1 adipocytes, CYP27A1 and CYP27B1 mRNA were detected in basal conditions and induced after D3 treatment. Pre-treatment of 3T3-L1 adipocytes not only with 1,25[OH]2D3, but also with D3 before inflammatory stimulation, significantly prevented the increase in gene expression and protein secretion of IL-6 and TNF-α, and significantly increased IL-10 mRNA and protein production compared with adipocytes treated only with lipopolysaccharide (LPS). Biological effects of D3 were still present after inhibition of P450 activity with ketokonazole. LPS determined a decrease in cell area compared with controls, paralleled by a significant increase in optical density (OD) of lipid droplets, whereas 1,25[OH]2D3 and D3 alone significantly increased adipocytes area and decreased OD. Pretreatment with both forms of vitamin D preserved cells from the reduction in their area observed after LPS treatment. LPS decreased more the area of cells grown in a high calcium medium than of adipocytes grown in a low calcium medium. In the presence of a high calcium medium, 1,25(OH)2D3 treatment preserved cell area, maintaining its anti-inflammatory and adipogenic properties. In conclusion our results show that D3, besides 1,25[OH]2D3, presents anti-inflammatory effects on 3T3-L1, as well as that adipocytes have the enzymatic pathways necessary to locally regulate the production of active forms of vitamin D, capable of influencing adipocyte phenotype and function.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Calcitriol; Calcium; Cholecalciferol; Gene Expression Regulation; Inflammation; Inflammation Mediators; Metabolic Networks and Pathways; Mice; Phenotype

Inflammation plays an essential role in the pathophysiology of atherosclerosis. Our study was aimed to investigate whether salvianolate, a novel water-soluble phenolic compound of Danshen, alleviates atherosclerosis via regulating the inflammation in rats. High fat diet feeding plus vitamin D3 injection was used to induce atherosclerosis in rats. Salvianolate (60, 120 or 240 mg/kg) or placebo was given to atherosclerotic rats. The plasma lipids, interleukin 6 (IL-6) and C reactive protein (CRP) were measured by ELISA. CD4+CD25+Foxp3+ cells were determined by flow cytometry. Histological changes were examined by hematoxylin and eosin staining. The results showed that the levels of plasma IL-6 and CRP were elevated in the rats fed on high fat diet, and the histological analysis demonstrated the successful establishment of atherosclerosis models. Treatment with salvianolate alleviated the atherosclerotic process and decreased the levels of plasma IL-6 and CRP. Also the number of CD4+CD25+Foxp3+ cells was increased in salvianolate-treated rats. It was concluded that salvianolate could treat atherosclerosis via modulating the inflammation at cytokine and cell levels.

Topics: Animals; Atherosclerosis; C-Reactive Protein; Cholecalciferol; Diet, High-Fat; Dose-Response Relationship, Drug; Flow Cytometry; Forkhead Transcription Factors; Inflammation; Interleukin-6; Lipids; Lymphocyte Count; Male; Phytotherapy; Plant Extracts; Rats, Wistar; Receptors, Complement 3b; Salvia miltiorrhiza; T-Lymphocytes, Regulatory; Vitamins

Vitamin D deficiency is common in the general population and even more prevalent in patients with chronic kidney disease (CKD). Low 25-hydroxyvitamin D [25(OH)D] levels have been associated with cardiovascular disease, though a definitive mechanistic link has not been established. Further, it is unclear if repleting vitamin D mitigates the excess risk observed in epidemiologic studies. Because vitamin D may regulate innate immunity and gut epithelial differentiation, we hypothesized that oral cholecalciferol (D3) would result in decreased blood endotoxin activity, a potential risk factor for cardiovascular disease. STUDY DESIGN, SETTING & PARTICIPANTS, INTERVENTION: We studied 12 stable outpatients with CKD stage 3 and 25(OH)D deficiency, who received D3 30,000 units weekly for 8 weeks. The primary endpoint was the change in blood endotoxin activity.. Baseline endotoxin activity correlated with 25(OH)D levels (r = -0.60, p = 0.04). Endotoxin activity decreased by 25% from baseline (p = 0.03). Despite the decrease in endotoxin activity, there was no change in intestinal permeability.. The results of this study suggest that vitamin D repletion therapy may have an effect on endotoxin activity in early CKD. Further intervention studies using vitamin D in the CKD population are required.

Topics: Aged; Biomarkers; Cholecalciferol; Cytokines; Endotoxins; Female; Humans; Inflammation; Intestinal Mucosa; Intestines; Male; Middle Aged; Permeability; Renal Insufficiency, Chronic; Vitamin D; Vitamin D Deficiency

Vitamin D is an important factor for calcium and phosphorus homeostasis. A negative relationship has been observed between vitamin D status and diseases such as cancer, arthritis, diabetes, and muscle fiber atrophy. However, the relationship between vitamin D and prevention of skeletal muscle damage has not been clearly elucidated. The purpose of this study was to investigate the effects of vitamin D on exercise-induced muscle changes. Rats were divided into 3 groups: (1) sedentary control (C: n=10), (2) high-intensity exercise (HE: n=10), and (3) high-intensity exercise with vitamin D supplementation (HED: n=10; i.p. 1000 IU/kg body weight). Rats were trained for 30 min/day on treadmills (5 days/week for 8 weeks) with the running speed gradually increased up to 30 m/min at a 3° incline. At the end of the training period, the running speed was 38 m/min at a 5° incline. The high-intensity exercise significantly increased plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity. In addition, IL-6 and TNF-α levels as well as phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB were significantly increased. Vitamin D-treated rats showed a significant decrease in plasma CK level, phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB, and gene expression of IL-6 and TNF-α. Furthermore, the protein expression of vitamin D receptor (VDR) was highly increased in the muscles of HED-treated rats, respectively. Therefore, we concluded that vitamin D may play a pivotal role in exercise-induced muscle damage and inflammation through the modulation of MAPK and NF-κB involved with VDR.

Topics: Animals; Biomarkers; Cholecalciferol; Creatine Kinase; Cytoplasm; Dietary Supplements; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Inflammation; Interleukin-6; L-Lactate Dehydrogenase; Male; MAP Kinase Signaling System; Muscle, Skeletal; NF-kappa B; Phosphorylation; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptors, Calcitriol; Tumor Necrosis Factor-alpha

To evaluate the effects of 25-hydroxycholecalciferol 25-[OH] D on bone mineral metabolism and inflammation parameters in hemodialysis patients.. The study was carried out at Hitit University Corum Education and Research Hospital, Corum, Turkey between July and September 2012. All of the 36 patients that underwent treatment in our hemodialysis unit were included in this study. Four patients were excluded from the study due to other complications. Of the remaining 32 patients, 28 patients mean age; 52+/- 18 years; 15 males and 13 females with a 25-OH vitamin D level of <30 ng/mL were included in the study. Four of the 32 remaining patients were excluded as their 25-OH vitamin D levels was >30 ng/ml. Patients with a 25-OH D level of <30 ng/mL were treated with 20,000 IU oral cholecalciferol once a week for 12 weeks. The level of vitamin D, mineral metabolism markers, and C-reactive protein CRP were evaluated.. After the treatment, the 25-OH D levels increased to >30 ng/mL in all patients 12.5+/-7.1 ng/mL versus 59.9+/-15.5 ng/mL; p<0.001. While there was a significant, but not life-threatening, increase in calcium levels 7.9 [7.26 to 8.32] mg/dL versus 8.48 [7.55 to 9.25] mg/dL, p<0.001, a statistically significant decrease was observed in CRP levels 9.34+/-4.4mg/L versus 4.4+/-1.6mg/L; p<0.001. Alkaline phosphatase, phosphorus, and parathyroid hormone levels did not change.. Vitamin D deficiency is a common problem in HD patients. Short-term weekly cholecalciferol treatment is safe and effective in this patient group, and cholecalciferol treatment had a positive effect on inflammatory markers.

Topics: Adult; Biomarkers; Cholecalciferol; Female; Humans; Inflammation; Male; Middle Aged; Minerals; Renal Dialysis; Turkey; Vitamin D Deficiency

The renin-angiotensin-aldosterone system (RAAS), vitamin D, and parathyroid hormone have all been implicated as regulators of adipocytokines and inflammation. We evaluated human interventional study protocols to investigate whether controlled modulations of these calcium- and sodium-regulatory hormones could influence adipocytokines and inflammation in obesity and diabetes.. Post-hoc analyses of two separate human protocols (Protocol 1, n=14; Protocol 2, n=24) conducted in a clinical research setting after rigorous control of diet, posture, medications, and diurnal rhythm, were performed. Protocol 1 evaluated obese hypertensives with vitamin D deficiency who received an infusion of angiotensin II (AngII) before and after 1month of vitamin D3 therapy. Protocol 2 evaluated obese subjects with type 2 diabetes who also received AngII. Adipocytokines and inflammatory markers were measured before and after vitamin D3 therapy, and also before and after infusions of AngII.. Vitamin D3 therapy significantly raised 25(OH)D and 1,25(OH)2D concentrations, and lowered parathyroid hormone, but had no effect on concentrations of adiponectin, resistin, leptin, IL-6, PAI-1, urinary TGFβ1, or HOMA-IR. AngII infusions, despite significant elevations in blood pressure and serum aldosterone, did not influence adipocytokine concentrations in either protocol.. In contrast to prior studies conducted in healthy populations, or those that could not control major regulators of the RAAS or adipocytokines, we observed that robust modulations in calcium- and sodium-regulatory hormones did not influence adipocytokines or inflammation in obesity or diabetes. Adipose-tissue physiology in these conditions may alter the hormonal regulation of inflammatory parameters.

Topics: Adipokines; Adult; Aged; Angiotensin II; Arterial Pressure; Biomarkers; Calcium; Cholecalciferol; Diabetes Mellitus; Female; Glycated Hemoglobin; Hormones; Humans; Inflammation; Infusions, Intravenous; Male; Middle Aged; Obesity; Renin-Angiotensin System; Resistin; Sodium; Young Adult

Vitamin D (25-hydroxyvitamin D, 25(OH)D) deficiency, hypovitaminosis D, is highly prevalent in chronic kidney disease patients and is potentially involved with complications in the hemodialysis (HD) population. The aim of this study was to evaluate the impact of cholecalciferol supplementation on biomarkers of mineral metabolism, inflammation, and cardiac function in a group of HD patients presenting with hypovitaminosis D and low intact parathyroid hormone (iPTH) levels.. HD patients with iPTH levels of <300 pg/mL, not receiving vitamin D therapy, and presenting with 25(OH)D levels of <30 ng/mL were enrolled in this prospective study. Oral cholecalciferol was prescribed once a week in the first 12 weeks (50,000 IU) and in the last 12 weeks (20,000 IU) of the study. High-sensitivity C-reactive protein, interleukin-6, and serum albumin were used as inflammatory markers. Echocardiograms were performed on a midweek interdialytic day at baseline and after 6 months of cholecalciferol supplementation.. In all, 30 patients were included in the final analysis. We observed a significant increase in serum 25(OH)D levels after 3 months (46.2 ± 14.4 ng/mL vs. 18.1 ± 6.6 ng/mL; P < .001) and after 6 months (40.4 ± 10.4 ng/mL vs. 18.1 ± 6.6 ng/mL; P < .001) of cholecalciferol supplementation. There were no significant changes in alkaline phosphatase, iPTH, phosphorus, and serum albumin levels, but there was a slight but significant increase in calcium levels after 6 months of cholecalciferol supplementation (9.4 ± 0.6 mg/dL vs. 9.0 ± 0.6 mg/dL; P = .02). Additionally, we observed a significant reduction in high-sensitivity C-reactive protein levels after 3 months (median: 0.62 [0.05 to 29.6] mg/L vs. 0.32 [0.02 to 3.13] mg/L; P = .02) and after 6 months (median: 0.62 [0.05 to 29.6] mg/L vs. 0.50 [0.02 to 5.66] mg/L; P = .04) of cholecalciferol supplementation, as well as a significant reduction in interleukin-6 levels (median: 6.44 pg/mL vs. 3.83 pg/mL; P = .018) after 6 months of supplementation. Left ventricular mass index was significantly reduced at the end of supplementation (159 ± 55 g/m(2) vs. 175 ± 63 g/m(2); P = .03).. Cholecalciferol supplementation in HD patients was found to be safe and efficient to correct hypovitaminosis D and established little impact on mineral metabolism markers. Additionally, we observed a reduction in important surrogate markers of cardiovascular risk, namely systemic inflammation and left ventricular hypertrophy, suggesting an anti-inflammatory action and possibly an improvement of cardiac dysfunction.

Topics: Aged; Alkaline Phosphatase; Biomarkers; C-Reactive Protein; Calcium; Cholecalciferol; Dietary Supplements; Female; Humans; Hyperparathyroidism; Inflammation; Interleukin-6; Male; Middle Aged; Myocardium; Parathyroid Hormone; Phosphorus; Prospective Studies; Renal Dialysis; Serum Albumin; Vitamin D; Vitamin D Deficiency; Vitamins

Allergen-specific immunotherapy (SIT) is currently the only curative treatment for allergy but the treatment needs to be improved. We hypothesize that covalent coupling of immunomodulating vitamin D3 to the major cat allergen Fel d 1 can enhance the beneficial effects of SIT to cat allergy.. We treated mice sensitized to Fel d 1 with subcutaneous injections of two doses of recombinant Fel d 1 coupled to 1α,25-dihydroxyvitamin D3 (rFel d 1:VD3) and compared to treatment with the same doses of rFel d 1 in a mouse model for cat allergy. Airway hyperresponsiveness (AHR), cytokines and cells in bronchoalveolar lavage (BAL), in vitro activation of splenocytes to rFel d 1, and Fel d 1-specific immunoglobulins were evaluated.. Treatment with both doses of rFel d 1:VD3 decreased AHR, cellular influx and Th2 cytokines in BAL compared to untreated mice. High- and low-dose rFel d 1 treatment also decreased AHR and BAL Th2 cytokines, with less decrease for the low-dose treatment. Importantly, the total number of cells and eosinophils in BAL was markedly reduced at both high- and low-dose rFel d 1:VD3 compared to treatment with rFel d 1 alone. Finally, treatment with both rFel d 1 and rFel d 1:VD3 induced Fel d 1-specific serum IgG.. Our results indicate a beneficial therapeutic effect of rFel d 1:VD3 on airway inflammation, AHR and rFel d 1-specific immune responses and thus suggest that this novel immunomodulatory candidate may improve both the efficacy and safety of SIT.

Topics: Allergens; Animals; Antibodies, Blocking; Bronchoalveolar Lavage; Cats; Chemotaxis, Leukocyte; Cholecalciferol; Desensitization, Immunologic; Disease Models, Animal; Eosinophils; Female; Glycoproteins; Humans; Hypersensitivity; Immunoglobulin A, Secretory; Immunoglobulin G; Inflammation; Interleukin-5; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Spleen

Male and female C57Bl6 mice were fed a control AIN76A diet, a new Western-style diet (NWD1) reflecting dietary patterns linked to elevated colon cancer incidence (higher fat, lower cholecalciferol, calcium, methyl donors, fiber), or NWD1 with elevated cholecalciferol and calcium (NWD2) from weaning. After 24 wk, serum 25-hydroxyvitamin D [25(OH)D] decreased by >80% in the NWD1 group compared with controls, but with no alteration in serum calcium or bone mineral density. The decreased serum 25(OH)D was prevented in the NWD2 group. After 32 wk, the NWD1 group compared with controls reduced overall energy expenditure by 15% without altering food consumption or physical activity and induced glucose intolerance, phenotypes associated with metabolic syndrome. These responses were unexpectedly exacerbated in the NWD2 group, further shifting mice toward greater fatty acid storage rather than oxidation compared with both control and NWD1 groups, but there was no change in physical activity, causing significant weight gain due to increased fat mass. The NWD1 group also exhibited inflammatory responses compared with controls, including macrophage-associated crown-like structures in epididymal adipose tissue and increased serum concentrations of the proinflammatory cytokine IL-1β, and of its targets, MCP-1 and Rantes, which were prevented or greatly mitigated in the NWD2 group. However, there was also elevated lipid storage in the liver and steatosis not seen in the control and NWD1 groups. Thus, elevating cholecalciferol and calcium in a Western-style diet can reduce inflammation associated with risk for colon tumor development, but interaction of nutrients in this diet can compromise liver function when fed long term.

Topics: Animal Feed; Animals; Blood Glucose; Bone Density; Calcium, Dietary; Chemokine CCL2; Chemokine CCL5; Cholecalciferol; Colonic Neoplasms; Eating; Energy Metabolism; Fatty Liver; Female; Inflammation; Insulin; Interleukin-1beta; Male; Mice; Mice, Inbred C57BL; Risk Factors; Vitamins

It is well known that high fat diets (HFDs) induce obesity and an increase in proinflammatory adipokines. Interleukin-6 (IL-6) is considered the major inflammatory mediator in obesity. Obesity is associated with a vitamin deficiency, especially of vitamins E and D3. We examined the effects of vitamin D3 and vitamin E supplementation on levels of IL-6 and IL-10 (as a marker of anti-inflammatory cytokines since, a balance between pro- and anti-inflammatory cytokines is maintained) protein expression in adipose tissue of mice provided with an HFD. Additionally, we measured the effects of vitamin E and vitamin D3 treatment on LPS-stimulated 3T3-L1 adipocytes IL-6 and IL-10 secretion.. IL-6 protein levels and the IL-6/IL-10 ratio were decreased in epididymal white adipose tissue in groups receiving vitamins E and D3 supplementation compared to the HFD group. A 24-hour treatment of vitamin D3 and vitamin E significantly reduced the IL-6 levels in the adipocytes culture medium without affecting IL-10 levels.. Vitamin D3 and vitamin E supplementation in an HFD had an anti-inflammatory effect by decreasing IL-6 production in epididymal adipose tissue in mice and in 3T3-L1 adipocytes stimulated with LPS. Our results suggest that vitamin E and D3 supplementation can be used as an adjunctive therapy to reduce the proinflammatory cytokines present in obese patients.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Adipose Tissue, White; alpha-Tocopherol; Animals; Cholecalciferol; Dietary Fats; Inflammation; Interleukin-10; Interleukin-6; Lipopolysaccharides; Male; Mice

Infectious tolerance is a term generally assigned to the process through which regulatory T cells (Tregs) transfer immunoregulatory properties to other T cells. In this study, we demonstrated that a similar process applies to human dendritic cells (DCs), albeit through a different mechanism. We induced and cloned proinsulin-specific Tregs using tolerogenic DCs and investigated mechanisms by which induced Ag-specific regulatory T cells (iaTregs) endorse the suppressive effects. iaTregs expressed FOXP3, programmed death-1, and membrane-bound TGF-β and upregulated IL-10 and CTLA-4 after stimulation with the cognate Ag. The iaTregs suppressed effector T cells only when both encountered the cognate Ags on the same APCs (linked suppression). This occurred independently of IL-10, TGF-β, programmed death-1, or CTLA-4. Instead, iaTregs used a granzyme B-mediated mechanism to kill B cells and monocytes, whereas proinflammatory DCs that resisted being killed were induced to upregulate the inhibitory receptors B7 (family) homolog 3 and ICOS ligand. These re-educated mature monocyte-derived dendritic cells (mDCs) suppressed effector T cells and induced IL-10-producing cells from the naive T cell pool. Our data indicated that human tolerogenic DCs confer infectious tolerance by inducing Ag-specific Tregs, which, in turn, re-educate proinflammatory mature DCs into DCs with regulatory properties.

Topics: Cell Differentiation; Cells, Cultured; Cholecalciferol; Clone Cells; Coculture Techniques; Dendritic Cells; Epitopes, T-Lymphocyte; Forkhead Transcription Factors; HLA-DRB1 Chains; Humans; Immune Tolerance; Inflammation; Inflammation Mediators; Interleukin-2 Receptor alpha Subunit; Lymphocyte Activation; Monocytes; Programmed Cell Death 1 Receptor; Proinsulin; T-Lymphocytes, Regulatory

Mast cell production of interleukin-10 (IL-10) can limit the skin pathology induced by chronic low-dose ultraviolet (UV)-B irradiation. Although the mechanism that promotes mast cell IL-10 production in this setting is unknown, exposure of the skin to UVB irradiation induces increased production of the immune modifying agent 1alpha,25-dihydroxyvitamin D(3) (1alpha,25[OH](2)D(3)). We now show that 1alpha,25(OH)(2)D(3) can up-regulate IL-10 mRNA expression and induce IL-10 secretion in mouse mast cells in vitro. To investigate the roles of 1alpha,25(OH)(2)D(3) and mast cell vitamin D receptor (VDR) expression in chronically UVB-irradiated skin in vivo, we engrafted the skin of genetically mast cell-deficient WBB6F(1)-Kit(W/W-v) mice with bone marrow-derived cultured mast cells derived from C57BL/6 wild-type or VDR(-/-) mice. Optimal mast cell-dependent suppression of the inflammation, local production of proinflammatory cytokines, epidermal hyperplasia, and epidermal ulceration associated with chronic UVB irradiation of the skin in Kit(W/W-v) mice required expression of VDR by the adoptively transferred mast cells. Our findings suggest that 1alpha,25(OH)(2)D(3)/VDR-dependent induction of IL-10 production by cutaneous mast cells can contribute to the mast cell's ability to suppress inflammation and skin pathology at sites of chronic UVB irradiation.

Topics: Animals; Bone Marrow Cells; Calcitriol; Cell Culture Techniques; Cells, Cultured; Cholecalciferol; Cytokines; Inflammation; Interleukin-10; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Pigmentation; Radiography; Receptors, Calcitriol; Skin; Skin Transplantation; Ultraviolet Rays

Many chronic inflammatory diseases are associated with increased risk of developing cancer. In the colon, strong support for a link between chronic inflammation and cancer extends, in part, from population-based studies of persons with inflammatory bowel disease (IBD). Patients with IBD are at increased risk of developing colorectal cancer (CRC). The general consensus is that IBD results from the combined effects of genetics and environment factors known to affect the immune system. Vitamin D, an important regulator of the immune system, has been linked to IBD. Despite the strong potential reported for 1,25-dihydroxyvitamin D (1,25-OH)2D), its effects on calcium metabolism limits its application. Recently, less active vitamin D metabolites, cholecalciferol and 25-hydroxyvitamin D (25(OH)D), have gained considerable attention as promising agents against IBD-related colon cancer. Yet, their anti-proliferative properties and mechanism of action remain to be better defined. We present several signaling pathways commonly regulated by vitamin D compounds and highlight their regulation on TLR4. The efficacy of 25(OH)D and 1alpha-hydroxyviatmin D5 are evaluated using the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced IBD-related colon carcinogenesis model. In summary, vitamin D supplementation may provide a cost-effective approach to reduce IBD related colon cancer.

Topics: Caco-2 Cells; Calcitriol; Cholecalciferol; Colonic Neoplasms; Dietary Supplements; Female; HCT116 Cells; HT29 Cells; Humans; Inflammation; Inflammatory Bowel Diseases; Models, Biological; Oligonucleotide Array Sequence Analysis; Toll-Like Receptor 4; Vitamin D

Vitamin D3 has diverse biological effects extending beyond the maintenance of calcium and phosphorus homeostasis and ensuring the proper functioning of the body.. This study evaluated the levels of vitamin D3 and its association with nutritional status, immunological activity, and selected markers of cardiovascular disease in patients on long-term hemodialysis (HD).. We measured 25-hydroxyvitamin D3 (25(OH)D3) levels in a group of 84 patients (mean age, 65 years; average time on dialysis, 32.5 months) and investigated correlations between 25(OH)D3 levels and the following parameters: albumin, body mass index, hemoglobin (Hb), interleukin 6 (IL-6), interleukin 10, C-reactive protein, asymmetric dimethylarginine (ADMA), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and comorbidity score.. A mean 25(OH)D3 level was 15.4 +/-7.2 ng/ml and only 5% of patients had 25(OH)D3 levels above the normal value of 30 ng/ml. There was no statistically significant difference in 25(OH)D3 levels between women and men (P = 0.06). A negative correlation was observed between 25(OH)D3 and IL-6 (R = -0.31, P = 0.009) and ADMA (R = -0.26, P = 0.03), as well as a positive correlation between 25(OH)D3 and Hb (R= 0.21, P = 0.05). There was no association between 25(OH)D3 levels and nutritional status.. A significant vitamin D3 deficiency observed in the majority of patients undergoing long-term HD contributes to the development of chronic inflammation, anemia, and indirectly, to endothelial cell injury.

Topics: Aged; Cardiovascular Diseases; Cholecalciferol; Female; Humans; Inflammation; Kidney Failure, Chronic; Male; Nutritional Status; Renal Dialysis; Vitamin D Deficiency

The process of aging is linked to oxidative stress, microglial activation, and proinflammatory factors, which are known to decrease cell proliferation and limit neuroplasticity. These factors may lead the transition from normal aging to more severe cognitive dysfunction associated with neurodegenerative diseases. We have shown that natural compounds such as polyphenols from blueberry and green tea and amino acids like carnosine are high in antioxidant and antiinflammatory activity that decreases the damaging effects of reactive oxygen species (ROS), in the blood, brain, and other tissues of the body. Furthermore, we have shown that the combination of these nutrients (called NT-020) creates a synergistic effect that promotes the proliferation of stem cells in vitro and in vivo. In the current study, we examined the effects of NT-020 on neurogenesis and performance on a Morris water maze (MWM). Aged (20-month-old) male Fischer 344 rats were treated with 135.0 mg/kg per day (n = 13) of NT-020. Young (3-month-old) (n = 10) and aged (20-month-old) (n = 13) control male Fischer 344 rats were treated with water by oral gavage. All groups were treated for a period of 4 weeks. Although there was no difference in performance in the MWM when comparing all aged rats, when the data for aged impaired rats were compared, there was a significant difference between groups on the last day of training with the treatment group performing better than controls. Using the cell cycle-regulating protein (Ki67), doublecortin (DCX), and OX6 antibody markers, cell proliferation, neurogenesis, and microglial activation were estimated in the dentate gyrus (DG) of young and aged animals. Cell proliferation was also examined in the subventricular zone (SVZ). A decreased number of OX6 MHC II-positive cells, increased neurogenesis, and increased number of proliferating cells were found in rats treated with NT-020 in comparison with aged control rats. In sum, NT-020 may promote health, proliferation, and maintenance of neurons in the age animals and exert antiinflammatory actions that promote function in the aged stem cell niche.

Topics: Aging; Animals; Carnosine; Cell Proliferation; Cholecalciferol; Cognition; Dentate Gyrus; Dietary Supplements; Doublecortin Domain Proteins; Doublecortin Protein; Inflammation; Ki-67 Antigen; Male; Memory; Microglia; Microtubule-Associated Proteins; Neural Stem Cells; Neurogenesis; Neuropeptides; Plant Extracts; Rats; Rats, Inbred F344

Vitamin D receptor (VDR), a nuclear receptor that regulates calcium homeostasis, has been found to function as a receptor for secondary bile acids. Because the in vivo role of VDR in bile acid metabolism remains unknown, we investigated the effect of VDR activation in a mouse model of cholestasis. We treated mice with 1alpha-hydroxyvitamin D(3) [1alpha(OH)D(3)] after bile duct ligation (BDL) and examined mRNA expression and cytokine levels. 1alpha(OH)D(3) treatment altered the expression of genes involved in bile acid synthesis and transport in the liver, kidney, and intestine but did not decrease bile acid levels in the plasma and liver of BDL mice. 1alpha(OH)D(3) treatment suppressed mRNA expression of proinflammatory cytokines in the liver and strongly decreased the plasma levels of proinflammatory cytokines in BDL mice. These findings indicate that 1alpha(OH)D(3) regulates a network of bile acid metabolic genes and represses proinflammatory cytokine expression in BDL mice. VDR ligands have the potential to prevent the cholestasis-induced inflammatory response.

Topics: Animals; Bile Acids and Salts; Bile Ducts; Biophysical Phenomena; Cholecalciferol; Female; Gene Expression; Inflammation; Mice; Mice, Inbred C57BL; Receptors, Calcitriol; Sterilization, Tubal

The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1) to form 20-hydroxycholecalciferol, which can induce growth arrest and differentiation of both primary and immortalized epidermal keratinocytes. Since nuclear factor-kappaB (NF-kappaB) plays a pivotal role in the regulation of cell proliferation, differentiation and apoptosis, we examined the capability of 20-hydroxycholecalciferol to modulate the activity of NF-kappaB, using 1,25-dihydroxycholecalciferol (calcitriol) as a positive control. 20-hydroxycholecalciferol inhibits the activation of NFkappaB DNA binding activity as well as NF-kappaB-driven reporter gene activity in keratinocytes. Also, 20-hydroxycholecalciferol induced significant increases in the mRNA and protein levels of the NF-kappaB inhibitor protein, IkappaB alpha, in a time dependent manner, while no changes in total NF-kappaB-p65 mRNA or protein levels were observed. Another measure of NF-kappaB activity, p65 translocation from the cytoplasm into the nucleus was also inhibited in extracts of 20-hydroxycholecalciferol treated keratinocytes. Increased IkappaB alpha was concomitantly observed in cytosolic extracts of 20-hydroxycholecalciferol treated keratinocytes, as determined by immunoblotting and immunofluorescent staining. In keratinocytes lacking vitamin D receptor (VDR), 20-hydroxycholecalciferol did not affect IkappaB alpha mRNA levels, indicating that it requires VDR for its action on NF-kappaB activity. Comparison of the effects of calcitrol, hormonally active form of vitamin D3, with 20-hydrocholecalciferol show that both agents have a similar potency in inhibiting NF-kappaB. Since NF-kappaB is a major transcription factor for the induction of inflammatory mediators, our findings indicate that 20-hydroxycholecalciferol may be an effective therapeutic agent for inflammatory and hyperproliferative skin diseases.

Topics: Cell Proliferation; Cholecalciferol; Cholesterol Side-Chain Cleavage Enzyme; Humans; Hydroxycholecalciferols; I-kappa B Proteins; Immunoblotting; Inflammation; Interleukin-1alpha; Keratinocytes; Mixed Function Oxygenases; Models, Biological; NF-kappa B; NF-KappaB Inhibitor alpha; Transcription Factors

The four choroid plexuses in the brain ventricles are not identical, but differences among them have rarely been studied. The present work concerns the inflammatory and hemorrhagic choroid plexitis produced in Lewis rats by a single gavage of cholecalciferol (vitamin D(3)) or related steroids with vitamin D activity. Plexitis was very severe in the fourth ventricular plexus, somewhat less severe in the lateral ventricular plexuses, and almost absent in the third ventricular plexus. These findings were compared to the scanty data from the literature on differences among the plexuses.

Topics: Animals; Cerebral Ventricles; Cholecalciferol; Choroid Plexus; Female; Inflammation; Male; Rats; Rats, Inbred Lew; Severity of Illness Index; Vitamins

Vitamin D insufficiency is widespread, regardless of geographical location. It is particularly prevalent in the elderly and has far-ranging health consequences including: osteoporosis, falls, increased risk of cancer, and altered glucose and lipid metabolism. Increasing evidence strongly supports the benefits of vitamin D supplementation and also reveals that present recommendations are inadequate, especially for older individuals. Although additional studies are still needed to further optimize diagnostic and therapeutic approaches, physicians should consider prescribing cholecalciferol--at least 2000 international units (IU) per day--to all elderly patients. Oral cholecalciferol supplementation at that level is inexpensive, safe, and effective, and has great potential to improve the quality of life of the elderly.

Topics: Accidental Falls; Aged; Cholecalciferol; Fractures, Bone; Humans; Inflammation; Metabolic Syndrome; Neoplasms; Osteoporosis; Ultraviolet Rays; Vitamin D; Vitamin D Deficiency; Vitamins

Toll-like receptors (TLR) represent an ancient front-line defence system that enables the host organism to sense the presence of microbial components within minutes. As inducers of inflammation, TLR act as important triggers of distinct entities such as sepsis or autoimmune disease exacerbation. We report here that vitamin D3 [1alpha,25-dihydroxycholecalciferol, 1,25(OH)(2)D3] suppresses the expression of TLR2 and TLR4 protein and mRNA in human monocytes in a time- and dose-dependent fashion. Despite 1,25(OH)(2)D3-induced up-regulation of CD14, challenge of human monocytes with either LPS or lipoteichoic acid resulted in impaired TNF-alpha and procoagulatory tissue factor (CD142) production, emphasizing the critical role of TLR in the induction of inflammation. Moreover, reduced TLR levels in 1,25(OH)(2)D3-treated phagocytes were accompanied by impaired NF-kappaB/RelA translocation to the nucleus and by reduced p38 and p42/44 (extracellular signal-regulated kinase 1/2) phosphorylation upon TLR-ligand engagement. Both TLR down-regulation and CD14 up-regulation were substantially inhibited by the vitamin D receptor (VDR) antagonist ZK 159222, indicating that the immunomodulatory effect of 1,25(OH)(2)D3 on innate immunity receptors requires VDR transcription factor activation. Our data provide strong evidence that 1,25(OH)(2)D3 primes monocytes to respond less effectively to bacterial cell wall components in a VDR-dependent mechanism, most likely due to decreased levels of TLR2 and TLR4.

Topics: Active Transport, Cell Nucleus; Calcitriol; Cells, Cultured; Cholecalciferol; Dose-Response Relationship, Drug; Down-Regulation; Humans; Inflammation; Lipopolysaccharide Receptors; Lipopolysaccharides; Macrophage Activation; Mitogen-Activated Protein Kinase 1; Monocytes; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Receptors, Calcitriol; Signal Transduction; Teichoic Acids; Toll-Like Receptor 2; Toll-Like Receptor 4; Transcription Factor RelA; Up-Regulation

One of the major challenges in neuroscience is to identify the changes which accompany aging and which contribute to the well-documented age-related deterioration in cognitive function. This is a particular challenge in the light of the vast array of reported changes, which include morphological changes like synaptic and perhaps cell loss, alteration in membrane composition and the resultant changes in function of membrane proteins, modulation of the hypothalamo-pituitary axis, impaired calcium homoeostatic mechanisms, alteration in enzyme function and decreased neurotransmitter release. In the past few years, evidence suggesting that an aged brain exhibits signs of oxidative stress and inflammatory stress has been accumulating, and recent evidence using microarray analysis has added support to this view. In this paper, we provide evidence to suggest that vitamin D3 acts as an anti-inflammatory agent and reverses the age-related increase in microglial activation and the accompanying increase in IL-1beta (interleukin-1beta) concentration.

Topics: Aging; Animals; Anti-Inflammatory Agents; Cholecalciferol; Disease Models, Animal; Hippocampus; Inflammation; Interleukin-1; Interleukin-10; Rats; Synapses

1[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) is a novel synthetic triterpenoid more potent than its parent compound, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), both in vitro and in vivo. CDDO-Im is highly active in suppressing cellular proliferation of human leukemia and breast cancer cell lines (IC(50), approximately 10-30 nM). In U937 leukemia cells, CDDO-Im also induces monocytic differentiation as measured by increased cell surface expression of CD11b and CD36. In each of these assays, CDDO-Im is several-fold more active than CDDO. Although CDDO and CDDO-Im both bind and transactivate peroxisome proliferator-activated receptor (PPAR) gamma, the irreversible PPARgamma antagonist GW9662 does not block the ability of either CDDO or CDDO-Im to induce differentiation; moreover, PPARgamma-null fibroblasts are still sensitive to the growth-suppressive effects of CDDO. Thus, CDDO-Im has significant actions independent of PPARgamma transactivation. In addition, the rexinoid LG100268 and the deltanoid ILX23-7553 (ILX7553) synergize with CDDO and CDDO-Im to induce differentiation. In vivo, CDDO-Im is a potent inhibitor of de novo inducible nitric oxide synthase expression in primary mouse macrophages. Moreover, CDDO-Im inhibits growth of B16 murine melanoma and L1210 murine leukemia cells in vivo. The potent effects of CDDO-Im, both in vitro and in vivo, suggest it should be considered for clinical use.

Topics: Animals; Antineoplastic Agents; CD11b Antigen; CD36 Antigens; Cell Differentiation; Cell Division; Cell Line, Tumor; Cell Separation; Cholecalciferol; Dose-Response Relationship, Drug; Female; Fibroblasts; Flow Cytometry; Humans; Imidazoles; Inflammation; Inhibitory Concentration 50; Mice; Models, Chemical; Monocytes; Neoplasms; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oleanolic Acid; Receptors, Cytoplasmic and Nuclear; Time Factors; Transcription Factors; Transcriptional Activation; U937 Cells

Human cartilage glycoprotein 39 (HC gp-39) has been described as a major secreted product of cultured articular chondrocytes, synovial fibroblasts, and the osteosarcoma line MG63. However, its expression in these cells types has not been directly linked to corresponding cell types in vivo. In this report, expression of HC gp-39 is demonstrated from peripheral blood-derived macrophages in association with their differentiation from monocytes to macrophages. Consistent with macrophage specificity, HC gp-39 expression is also induced upon selective stimulation of the pluripotent promyelocytic leukemia cell line HL-60 toward the monocyte/macrophage lineage with vitamin D3 or phorbol 12-myristate 13-acetate (PMA), while treatments stimulating granulocyte and eosinophilic pathways do not induce expression. Furthermore, HC gp-39 expression levels correlate with the degree of morphological differentiation induced by PMA and vitamin D3 treatments. PMA-induced mRNA expression occurs by 36 h and is a secondary transcriptional response since its synthesis is inhibited by cycloheximide. Apparently, HC gp-39 expression is tied to later events in the differentiation of monocytes into macrophages. The in vivo significance of these results is validated by the in situ detection of HC gp-39 mRNA in inflammatory macrophages associated with rheumatoid synovium. Thus, macrophages appear to be an important source of HC gp-39, which has been shown to be present at elevated levels in the blood and synovium of rheumatoid arthritis patients. The implications of this extend well beyond the previously restricted observations in cell types associated with the joint and suggest a potential involvement of macrophage-derived HC gp-39 in other aspects of inflammation, tissue remodeling, and host defense.

Topics: Adipokines; Arthritis, Rheumatoid; Cartilage, Articular; Cell Differentiation; Cell Line; Cells, Cultured; Chitinase-3-Like Protein 1; Cholecalciferol; Cycloheximide; Glycoproteins; HL-60 Cells; Humans; Inflammation; Jurkat Cells; Kinetics; Lectins; Macrophages; Monocytes; Polymerase Chain Reaction; Recombinant Proteins; Reference Values; RNA, Messenger; Synovial Membrane; Tetradecanoylphorbol Acetate; Transcription, Genetic

When rat peritoneal nonadherent cells were treated with inflammatory lipid metabolites and cultured with adherent cells in 1% fetal calf serum (FCS) supplemented medium RPMI 1640 (FCS medium) for 3 hr, markedly enhanced phagocytic and superoxide generating capacities of macrophages were observed. Stepwise preparation of conditioned medium of lysophosphatidylcholine (lyso-Pc)-treated B cells and untreated T cells in FCS medium generated a potent macrophage activating factor whereas cultivation of lyso-Pc-treated B cells alone in a 1% adult rat serum supplemented medium efficiently generated the macrophage activating factor. Generation of macrophage activating factor requires a precursor protein, serum vitamin D3-binding protein (DBP), as well as participation of lymphocyte glycosidases. The lyso-Pc-inducible beta-galactosidase of B lymphocytes and the Neu-1 sialidase of T lymphocytes modified bovine DBP (bDBP) to yield the macrophage activating factor, a protein with N-acetylgalactosamine as the remaining sugar. In contrast, lyso-Pc-inducible beta-galactosidase of B cells alone modified rat DBP (rDBP) to yield the macrophage activating factor, a protein with N-acetylgalactosamine as the remaining sugar. Thus, we conclude that bDBP carries a trisaccharide composed of N-acetylgalactosamine, galactose, and sialic acid while rDBP carries a disaccharide composed of N-acetylgalactosamine and galactose.

Topics: Animals; B-Lymphocytes; Biological Factors; Cattle; Cholecalciferol; Culture Media, Conditioned; Glycerides; Glycoside Hydrolases; Inflammation; Laurates; Lysophosphatidylcholines; Macrophage Activation; Macrophages, Peritoneal; Monoglycerides; Neuraminidase; Protein Precursors; Rats; Rats, Inbred F344; Signal Transduction; T-Lymphocytes; Vitamin D-Binding Protein

A proinflammatory cytokine cascade, including IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, and IL-8, is activated in response to infection or immunologic insult. Besides their immunologic effects, several of these mediators stimulate bone resorption and inhibit bone formation. Osteocalcin, the most abundant noncollagenous protein present in bone, is an osteoblast-specific product whose production closely correlates with bone formation, and which has also been implicated in control of bone resorption. IL-1 and TNF have previously been shown to down-regulate osteocalcin production in vitro and in vivo, although the mechanism of this inhibition is unknown. In the present studies, IL-1 beta and TNF-alpha both inhibited 1,25-dihydroxyvitamin D3-stimulated production of osteocalcin protein and mRNA by ROS 17/2.8 osteosarcoma cells, whereas IL-6 had no effect on protein and only weakly inhibited mRNA. To determine if down-regulation was exerted at the transcriptional level, an osteocalcin promoter-chloramphenicol acetyltransferase (CAT) fusion gene was constructed (PHOC-CAT). After transient transfection of PHOC-CAT into ROS 17/2.8 osteosarcoma cells, reporter CAT activity was up-regulated by vitamin D at concentrations above 10(-12) M. In screening studies, TNF-alpha (-57%) and IL-6 (-37%) inhibited vitamin D-stimulated osteocalcin transcription, whereas IL-1 alpha, IL-1 beta, and IL-8 had no effect. Other immune cytokines and growth factors, including IL-2, IL-3, IL-7, and M-CSF, also failed to regulate osteocalcin transcription. Despite their lack of promoter regulation, IL-1 alpha and IL-1 beta also stimulated PGE2 production by ROS 17/2.8, further confirming the ability of the host cell to respond to these mediators. In dose-response experiments, down-regulation by TNF-alpha was significant at concentrations as low as 0.14 pM (0.1 U/ml), whereas approximately 10(4)-fold higher concentration of IL-6 was required to exert a similar effect. TNF-alpha-mediated down-regulation was unaffected by indomethacin. These data demonstrate that of these cytokines, TNF-alpha alone potently down-regulates osteocalcin promoter function, whereas IL-1 acts post-transcriptionally, possibly by reducing mRNA stability. Heterogeneity therefore exists among the proinflammatory cytokines with respect to the level at which control of osteocalcin expression is exerted.

Topics: Cell Line; Cholecalciferol; Cytotoxicity, Immunologic; Dinoprostone; Gene Expression Regulation; Genes; In Vitro Techniques; Indomethacin; Inflammation; Interleukin-1; Interleukin-6; Osteocalcin; Promoter Regions, Genetic; RNA, Messenger; Tumor Necrosis Factor-alpha

Our in vitro studies demonstrate that normal human epidermal melanocytes become swollen and more dendritic with an increase in amount of immunoreactive tyrosinase when they are cultured for several days with arachidonic acid metabolites, vitamin D3 or histamine. From these data we propose the following possible mechanisms for hyperpigmentations noted at postinflammatory sites and suntanned areas as well as at skin lesions of urticaria pigmentosa. Arachidonic acid metabolites and histamine, which are found in increased amounts in inflammatory skin, are thought to play a key role in the induction of postinflammatory hyperpigmentation. In sunburnt skin the increased proinflammatory mediators, particularly arachidonic acid metabolites, are also thought to stimulate melanocytes in the production of hyperpigmentation. Thus tanning after sun exposure may be induced not only by the effect of vitamin D3 and direct UV irradiation on the melanocytes but also by the effect of various arachidonic acid metabolites which are increased in sunburnt skin. Mast cells massively proliferate in the skin lesions of urticaria pigmentosa. Thus hyperpigmentation in the skin lesions of urticaria pigmentosa is quite likely to be induced by the chemical mediators, including histamine and leukotrienes, that are released from these cells.

Topics: Arachidonic Acids; Cells, Cultured; Cholecalciferol; Histamine; Humans; Inflammation; Melanins; Melanocytes; Skin; Skin Pigmentation; Sunburn; Time Factors; Urticaria Pigmentosa

Vitamin D3 deficient (D-) mice show a depressed inflammatory response and both inflammatory peritoneal macrophages and bone marrow polymorphonuclear leukocytes of D- mice exhibit a decreased spontaneous migration under agarose. The impaired phagocytic response of peritoneal macrophages from D- mice can be corrected by incubation with 1,25-dihydroxyvitamin D3 and is not affected by interaction with other vitamin D3 metabolites. Transfer of mice from the D- to the D+ state results in correction of both the inflammatory and the phagocytic response. Intactness of phagocyte function is thus directly dependent on vitamin D3 metabolism.

Topics: Animals; Ascitic Fluid; Bone Marrow Cells; Calcitriol; Cell Migration Inhibition; Cells, Cultured; Cholecalciferol; Inflammation; Macrophages; Male; Mice; Mice, Inbred BALB C; Neutrophils; Phagocytosis; Thioglycolates; Vitamin D Deficiency