laminaran and Inflammation

Damp conditions indoors favour the growth of microorganisms, and these contain several agents that may cause inflammation when inhaled. Moulds contain a polyglucose in their cell wall, defined as (1-->3)-beta-D-glucan, exhibiting effects on inflammatory cells.. The aim of the present study was to evaluate whether an inhalation challenge to purified (1-->3)-beta-D-glucan (grifolan) in humans could induce effects on inflammatory markers in blood, and to evaluate whether the reactions were related to the home exposure to (1-->3)-beta-D-glucan.. Seventeen subjects in homes with high levels of airborne (1-->3)-beta-D-glucan (G-high) and 18 subjects in homes with low levels of (1-->3)-beta-D-glucan (G-low) underwent two randomised, double-blind inhalation challenges, one to (1-->3)-beta-D-glucan suspended in saline and one to saline alone. A blood sample was taken before and after the challenges, and differential cell count, granulocyte enzymes in serum and the secretion of cytokines from peripheral blood mononuclear cells (PBMC) were measured.. Inhalation challenge with (1-->3)-beta-D-glucan induced a decrease in the secretion of tumour necrosis factor alpha from endotoxin-stimulated PBMC in the G-high group as well as in the G-low group. In the G-high group, the inhalation of (1-->3)-beta-D-glucan induced an increase in blood lymphocytes that was significantly different from the saline-induced effect.. The results suggest that an inhalation challenge to (1-->3)-beta-D-glucan has an effect on inflammatory cells and this effect may be related to a chronic exposure to moulds at home.

Topics: Adult; Aged; Air Pollution, Indoor; Animals; beta-Glucans; Bronchial Provocation Tests; Cytokines; Double-Blind Method; Glucans; Humans; Inflammation; Inhalation Exposure; Interleukin-10; Leukocytes, Mononuclear; Lipopolysaccharides; Lymphocyte Count; Middle Aged; Tumor Necrosis Factor-alpha

Repeated exposure to fungi-contaminated dust can lead to multiple adverse effects on the lung, such as hypersensitivity pneumonitis, granuloma even irreversible fibrosis. 1,3-β-glucan, a major cell wall component of fungi, is considered as its exposure biomarker. Existing studies showed that a series of Th responses were involved in 1,3-β-glucan induced hypersensitivity pneumonitis, in which macrophages, Treg, and IL-10 producing B cells were reported to participate. The reciprocal interaction among those critical immune cells in 1,3-β-glucan induced inflammation was not investigated yet. To clarify the regulatory mechanism of IL-10 producing B cells on Th and Treg, the current study set up a primary cell co-culture system. The anti-CD22 antibody was injected intraperitoneally to generate IL-10 producing B cells deficiency mouse model. Cells were isolated and purified from C57BL∖6 mice in different groups. Flow cytometry was used to check the phenotype of different cell subtypes. CBA assay and real-time PCR were used to examine the levels of multiple cytokines. Our results indicated that IL-10 producing B cells could modulate the 1,3-β-glucan induced inflammatory response. The modulation of IL-10 producing B cells on Th response after 1,3-β-glucan treatment was cell contact independent. What's more, the modulation pattern of IL-10 producing B cells might be impaired without Treg response. IL-10-producing B cells regulated 1,3-β-glucan induced Th responses in co-ordination with Treg cells.

Topics: Animals; B-Lymphocytes; beta-Glucans; Biomarkers; Cell Communication; Cytokines; Disease Susceptibility; Female; Immunomodulation; Immunophenotyping; Inflammation; Interleukin-10; Mice; Models, Biological; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

The dynamic ability of adipocytes in adipose tissue to store lipid in response to changes in the nutritional input and inflammatory elicitors has a major impact on human health. Previously, we established laminarin-coated beads or LCB as an inflammatory elicitor for adipocytes. However, it was not clear whether LCB inhibits lipid accumulation in adipocytes. Here, we show that LCB acts in the early stage of adipogenesis through both interleukin-1 receptor-associated kinases (IRAK) and spleen tyrosine kinase (SYK) pathways, resulting in the activation of the AMP-activated protein kinase (AMPK) and nuclear factor-κB (NF-κB) complexes, which subsequently cause cell cycle arrest, downregulation of the key transcription factors and enzymes responsible for adipogenesis, inhibition of adipogenesis, and stimulation of an inflammatory response. While LCB could effectively block lipid accumulation during the early stage of adipogenesis, it could stimulate an inflammatory response at any stage of differentiation. Additionally, our results raise a possibility that toll-like receptor 2 (TLR2) and C-type lectin domain family 7 member A (CLEC7A/Dectin-1) might be potential β-glucan receptors on the fat cells. Together, we present the mechanism of LCB, as fungal-like particles, that elicits an inflammatory response and inhibits adipogenesis at the early stage of differentiation.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; AMP-Activated Protein Kinases; Animals; Cell Cycle Checkpoints; Glucans; Inflammation; Mice; NF-kappa B; Transcription Factors

Adipose-derived stem cells (ADSCs) have anti-inflammatory and regenerative properties. The purpose of this study was to investigate the effect of locally administered ADSCs in a rheumatoid arthritis (RA) mouse model. In an in vivo experiment, single-cell ADSCs and three dimensionally-cultured ADSC spheroids were injected intra-articularly into the knees of RA model mice and histologically assessed. Marked improvement of synovial inflammation and articular cartilage regeneration was found in ADSC-treated mice. Proliferation, migration, and apoptosis assays of synovial fibroblasts incubated with single-cell and spheroid ADSCs were performed. The expression levels of total cytokine RNA in ADSC single cells, spheroids, and ADSC-treated inflammatory synovial fibroblasts were also evaluated by quantitative reverse transcription PCR. ADSCs suppressed the proliferation and migration of activated inflammatory cells and downregulated inflammatory cytokines. TSG-6 and TGFβ1 were significantly upregulated in ADSCs compared to controls and TGFβ1 was significantly upregulated in ADSC spheroids compared to single cells. The apoptosis rate of ADSC spheroids was significantly lower than that of single-cell ADSCs. These results indicated that intra-articular administration of ADSC single cells and spheroids was effective in an RA mouse model, offering a novel approach for the development of effective localized treatments for patients with RA.

Topics: Adipose Tissue; Animals; Arthritis, Rheumatoid; Cartilage, Articular; Cell Adhesion Molecules; Cell Movement; Cell Proliferation; Disease Models, Animal; Female; Fibroblasts; Glucans; Inflammation; Macrophages; Mice, Inbred BALB C; Regeneration; Spheroids, Cellular; Stem Cell Transplantation; Synovial Membrane; Transforming Growth Factor beta1; Up-Regulation

Laminarin is a polysaccharide isolated from brown algae that has various biological and pharmacological activities, such as antioxidant and anti-inflammatory properties. We recently reported that pretreated laminarin exerted neuroprotection against transient forebrain ischemia/reperfusion (IR) injury when we pretreated with 50 mg/kg of laminarin once a day for seven days in adult gerbils. However, there have been no studies regarding a neuroprotective effect of pretreated laminarin against IR injury in aged animals and its related mechanisms. Therefore, in this study, we intraperitoneally inject laminarin (50 mg/kg) once a day to aged gerbils for seven days before IR (5-min transient ischemia) surgery and examine the neuroprotective effect of laminarin treatment and the mechanisms in the gerbil hippocampus. IR injury in vehicle-treated gerbils causes loss (death) of pyramidal neurons in the hippocampal CA1 field at five days post-IR. Pretreatment with laminarin effectively protects the CA1 pyramidal neurons from IR injury. Regarding the laminarin-treated gerbils, production of superoxide anions, 4-hydroxy-2-nonenal expression and pro-inflammatory cytokines [interleukin(IL)-1β and tumor necrosis factor-α] expressions are significantly decreased in the CA1 pyramidal neurons after IR. Additionally, laminarin treatment significantly increases expressions of superoxide dismutase and anti-inflammatory cytokines (IL-4 and IL-13) in the CA1 pyramidal neurons before and after IR. Taken together, these findings indicate that laminarin can protect neurons from ischemic brain injury in an aged population by attenuating IR-induced oxidative stress and neuroinflammation.

Topics: Animals; Brain Ischemia; Cytokines; Disease Models, Animal; Gerbillinae; Glucans; Hippocampus; Inflammation; Male; Nerve Tissue Proteins; Neurons; Neuroprotection; Neuroprotective Agents; Oxidative Stress; Reperfusion Injury; Superoxide Dismutase

Adipocytes from white-adipose tissue are known to produce inflammatory cytokines, which play a major role in energy balance and metabolism. While they can respond to pathogen-associated molecular pattern (PAMPs) such as lipopolysaccharide (LPS) from bacteria, it is not known whether adipocytes can be stimulated by fungal cells. Previously, adipocytes were shown to produce toll-like receptor 2 (TLR2), a β-glucan receptor, suggesting that they could respond to β-glucan on the fungal cell wall. In this study, we show that heat-killed yeast induce an inflammatory response in adipocytes. Using fungal-like particles, namely laminarin-coated beads (LCB), we find that these particles trigger the expression of many key inflammatory genes in dose- and time-dependent fashions in adipocytes. These results suggest that β-glucan on the fungal cell wall is sufficient to elicit an inflammatory response in adipocytes. In addition, we show that both LCB and LCB-treated conditioned medium from RAW 264.7 murine macrophages (LCB-RM) induce the expression of those inflammatory genes through IKKβ-IκBα proteins. Together, we conclude that the fungal-like particles and the conditioned medium elicit an inflammatory response in adipocytes through the canonical or classical NF-κB pathway.

Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue, White; Animals; beta-Glucans; Culture Media, Conditioned; Cytokines; Glucans; Inflammation; Lipopolysaccharides; Macrophages; Mice; NF-kappa B; NF-KappaB Inhibitor alpha; Signal Transduction; Tumor Necrosis Factor-alpha

Topics: Adipose Tissue; Animals; Atherosclerosis; Computer Simulation; Diet, High-Fat; Fatty Liver; Glucans; Humans; Indazoles; Inflammation; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Monocytes; Nanoparticles; Obesity; Plaque, Atherosclerotic; Propionates

Cancer incidence continues to be a major health problem possibly because cancer is a complex system comprising many agents that interact in a non-linear manner resulting in many possible outcomes. The degree of complexity of a cancer system could be vast involving multiple endogenous and exogenous agents interacting with the over 10 trillion cells comprising the body. It is hypothesized that the practical management of this complexity may be a key to cancer prevention and possibly treatment. But the management and resolution of such an immensely complex system is difficult and may require a multidisciplinary approach including physics, biology, biochemistry and medical science. Research such as in systems biology involving large data sets may offer resolution in time, but the scale of the task is daunting. In evaluating the hypothesis, this paper proposes a method of resolution of the complex cancer system through a proxy in the form of the vital body system, energy balance, involved in several cancer processes. Although I suggest that the energy balance system is itself complex, it may permit access to factors that may be used in limiting cancer initiation. Meta-analysis related to factors of blood sugar, inflammation, stress and immune response reveal that they could be likely candidates for management. Analysis also reveals certain devices that may give practical effect to these management options. Due to the inherent complexity of a cancer system, multiple devices may need to be applied in a combination. The analysis suggests that the low-risk and low-cost devices metformin, vitamin D and vitamin C, may prove to be suitable for use as a practical cancer prevention strategy. If the presented hypothesis is correct, a practical method for prevention or management of cancer may be possible. A trial to test the hypothesis is proposed.

Topics: beta-Glucans; Decision Support Techniques; Diet; Drug Synergism; Energy Metabolism; Exercise; Glucose; Homeostasis; Humans; Inflammation; Melatonin; Meta-Analysis as Topic; Metformin; Models, Biological; Neoplasms; Stress, Physiological; Systems Theory; Vitamins

β-glucans are widely-known immunostimulants that are profusely used in aquaculture industry. The present study was conducted to evaluate the effect of different in-feed doses of β-1,3/1,6-glucans on the expression of antioxidant and stress-related genes (GST, HSP-70, Vtg), inflammation related genes (Il-8, TNFα, CXC-chemokine and CAS) and adaptive immune-related genes (MHC-IIβ, TLR-7, IgM-H, and Mx) of Oreochromis niloticus challenged and non-challenged with Streptococcus iniae. Six experimental groups were established: non-challenged control (non-supplemented diet), challenged control (non-supplemented diet), non-challenged supplemented with 0.1% β-glucan, challenged supplemented with 0.1% β-glucan, non-challenged supplemented with 0.2% β-glucan and challenged supplemented with 0.2% β-glucan. Fish were fed with β-glucan for 21 days prior challenge and then sampled after 1, 3 and 7 days post-challenge. In non-challenged group, variable effects of the two doses of β-Glucans on the expression of the studied genes were observed; 0.1% induced higher expression of HSP70, CXC chemokine, MHC-IIβ and MX genes. Meanwhile, 0.2% induced better effect on the expression of Vtg, TNF-α, CAS and IgM-H, and almost equal effects of both doses on GST and IL8. However, with the challenged group, 0.2% β-Glucans showed better effect than 0.1% at day one post challenge through significant up-regulation of GST, HSP, IL8, TNF-α, CXC, and MHC-IIβ, meanwhile, the effect of 0.1% was only on the expression of HSP70, MHC-IIβ, and TLR7 at day 3 post challenge. No stimulatory role for both doses of β-Glucans on the expression of almost all genes at day 7 post-challenge. We conclude that both doses of β-glucan can modulate the antioxidant, inflammation, stress and immune-related genes in Nile tilapia, moreover, 0.2% β-Glucans showed better protective effect with Streptococcus iniae challange.

Topics: Adjuvants, Immunologic; Animal Feed; Animals; Antioxidants; beta-Glucans; Cichlids; Diet; Dietary Supplements; Dose-Response Relationship, Drug; Fish Diseases; Immunity, Innate; Inflammation; Streptococcal Infections; Streptococcus iniae; Stress, Physiological

Binding of beta 1,3/1,6 glucan of Ganoderma lucidum (G. lucidum) with the receptor results in a series of signal transfers (signalling cascades), which activates the transcription factors for regulating inflammation. Excess cholesterol intake leads to an increase in the distance between fat cells and capillaries, which may cause hypoxia in the fat tissue of obese mice. This hypoxia induces the death of fat cells, resulting in the inflammation of adipose tissue or an increase in the inflammatory gene expression associated with obesity.. The current study examined the immunomodulation effect of G. lucidum beta 1,3/1,6 glucan according to immunoglobulin, poly-Ig receptor expression, Nature Killer cell (NK cell) activity, lymphocytes proliferation and cytokines expression.. Our present study shows that feeding G. lucidum beta 1,3/1,6 glucan to mice induces IgA or IgG expression in the serum and small intestine washing fluid and enhances poly-Ig receptor expression in the small intestine moreover, the observation of the IL-2 and Nature killer cell activity were exchanged.. The effect of a high-cholesterol diet in the inflammatory response was observed in heart, liver, kidney, spleen, and colon tissues through histopathological evaluations. The presented evidence demonstrates that the inflammation response in the high-cholesterol diet group was much higher than in the other groups and the beta 1,3/1,6 glucan reduces inflammation in obese mice fed a high-cholesterol diet.

Topics: Animals; beta-Glucans; Cholesterol, Dietary; Diet, High-Fat; Immunoglobulin A; Immunoglobulin G; Immunologic Factors; Inflammation; Intestine, Small; Kidney; Killer Cells, Natural; Liver; Male; Mice; Mice, Inbred C57BL; Myocardium; Receptors, Polymeric Immunoglobulin; Reishi

The anti-inflammatory effect on contact dermatitis of the water solubilized 1'-Acetoxychavicol Acetate (ACA) by complexation with β-1,3-glucan isolated form Aureobasidium pullulans black yeast is reported. It is well-known that ACA possesses a function to inhibit the activation of NF-κB by which genes encoding proinflammatory cytokines, chemokines, and growth factors are regulated. However, because ACA is quite insoluble in water, its usefulness has been extremely limited. On the other hand, a triple-helical polysaccharide β-1,3-glucan can include hydrophobic compounds into intrastrand hydrophobic cavity and solubilize poorly water-soluble compounds. In this study, solubilization of ACA by complexation with highly branched β-1,3-glucan was achieved. The effect of anti-inflammatory response of water-soluble ACA complex with β-1,3-glucan was confirmed in vitro and in vivo.

Topics: Animals; Anti-Inflammatory Agents; Benzyl Alcohols; beta-Glucans; Cell Line; Cytokines; Dermatitis, Contact; Dinitrofluorobenzene; Drug Stability; Immunohistochemistry; Inflammation; Lipopolysaccharides; Male; Mice, Inbred BALB C; NF-kappa B; Nitrates; Nitrites; Solubility; Solutions; Tumor Necrosis Factor-alpha; Water

Infection and inflammation suppress the expression and activity of several drug transporters in liver. In the intestine, P-glycoprotein (P-gp/MDR1), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) are important barriers to the absorption of many clinically important drugs. The expression and activity of these proteins were examined under inflammation. Drug transport was determined in jejunum and ileum segments isolated from 1.0 mg/kg, 5.0 mg/kg, and 7.5 mg/kg indomethacin-treated or control rats in diffusion chambers. Transport of laminaran, used as a model compound of (1-3) β-D-glucan, was measured for 120 min in the presence or absence of inhibitors. Reverse transcription-polymerase chain reaction was used to measure mRNA levels. Compared with controls, levels of Mdr1a mRNA were significantly decreased in the jejunum and ileum of 7.5 mg/kg indomethacin-treated rats. Both reductions in the basolateral to apical efflux of laminaran and increases in the apical to basolateral influx of laminaran were observed, resulting in significant increases in the apical to basolateral absorption of laminaran in 7.5 mg/kg indomethacin-treated rats. The inhibitory effect of verapamil on laminaran transport was observed in control rats but not in indomethacin-treated rats. Fluorescein isothiocyanate dextran 40,000 permeability, membrane resistance, and claudin-4 mRNA level were not altered, indicating no change in the paracellular pathway. These results indicate that indomethacin-induced inflammation reduces the intestinal expression and activity of P-gp in rats, which elicits corresponding changes in the intestinal transport of laminaran. Hence, inflammatory diseases may impose variability in drug bioavailability through alterations in the intestinal expression and activity of drug transporters.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; beta-Glucans; Biological Transport; Disease Models, Animal; Down-Regulation; Glucans; Ileum; Indomethacin; Inflammation; Intestinal Absorption; Jejunum; Male; Proteoglycans; Rats, Wistar; RNA, Messenger; Time Factors

1,3-β-glucan is considered a fungal biomarker and exposure to this agent induces lung inflammation. Previous studies have shown that 1,3-β-glucan affects Th1 and Th2 immune responses. Interleukin (IL)-10 and transforming growth factor (TGF)-β, as typical anti-inflammatory cytokines, suppress the Th1 immune response. To investigate the effects of 1,3-β-glucan on the secretion of cytokines in co-cultured mouse macrophages and lymphocytes in vitro, mice were exposed to 1,3-β-glucan or phosphate-buffered saline (PBS) by intratracheal instillation. Following extraction and co-culture of macrophages and lymphocytes, which were treated with or without 1,3-β-glucan in vitro, enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of cytokines and real-time reverse transcription (RT)-polymerase chain reaction (PCR) was used to investigate the mRNA expression of forkhead box p3 (Foxp3) in the cells. We showed that 1,3-β-glucan exposure in vitro decreased the secretion of Th1 cytokines and increased the secretion of Th2 cytokines in the culture media. Furthermore, 1,3-β-glucan exposure in vitro increased the secretion of IL-10 and TGF-β in the culture media. According to these results, 1,3-β-glucan exposure in vitro is suggested to promote the secretion of anti-inflammatory cytokines, which may lead to a decrease in the levels of Th1 cytokines and an increase in the levels of Th2 cytokines. 1,3-β-glucan is suggested to induce regulatory lymphocytes, which partly contributes to an increased secretion of anti-inflammatory cytokines in co-cultured mouse macrophages and lymphocytes in vitro.

Topics: Animals; beta-Glucans; Cytokines; Female; Forkhead Transcription Factors; Gene Expression Regulation; Inflammation; Macrophages; Mice; Th1 Cells; Th2 Cells

Interleukin-23 (IL-23), a cytokine produced primarily by dendritic cells, is involved in host defense against gut pathogens and promotes innate immunity and inflammatory responses through the IL-23/interleukin-17 axis. We previously reported that extracts from edible mushrooms enhanced antimicrobial α-defensin production n HL60 cells. Because IL-23 is involved in defensin production, we hypothesized that edible mushrooms may modulate its secretion and gut inflammation. Eight-week-old C57BL/6 mice were fed the AIN76 diet or the same diet supplemented with 5% white button (WBM), portabella, or shiitake mushrooms. To assess in vivo and in vitro cytokine secretion, 7 to 8 mice per group received 3% dextran sodium sulfate (DSS) in drinking water during the last 5 days of the 6-week feeding period. To delineate the mechanisms by which mushrooms alter IL-23 secretion, J.744.1 cells were incubated with (100 μg/mL) WBM, portabella, and shiitake extracts without and with 100 μg/mL curdlan (a dectin-1 agonist) or 1 mg/mL laminarin (a dectin-1 antagonist). The dectin-1 receptor is a pattern-recognition receptor found in phagocytes, and its activation promotes antimicrobial innate immunity and inflammatory responses. In DSS-untreated mice, mushrooms significantly increased IL-23 plasma levels but decreased those of interleukin-6 (IL-6) (P < .05). In DSS-treated mice, mushroom-supplemented diets increased IL-6 and IL-23 levels (P < .05). Mushroom extracts potentiated curdlan-induced IL-23 secretion, and mushroom-induced IL-23 secretion was not blocked by laminarin in vitro, suggesting the involvement of both dectin-1-dependent and dectin-1-independent pathways. Although all mushrooms tended to increase IL-6 in the colon, only WBM and shiitake tended to increase IL-23 levels. These data suggest that edible mushrooms may enhance gut immunity through IL-23.

Topics: Animals; Anti-Infective Agents; beta-Glucans; Cell Line; Colitis; Dextran Sulfate; Dietary Supplements; Female; Glucans; Immunity, Innate; Inflammation; Interleukin-17; Interleukin-23; Interleukin-6; Lectins, C-Type; Macrophages; Mice; Mice, Inbred C57BL; Organ Size; Polysaccharides; Regression Analysis; Shiitake Mushrooms; Thymus Gland; Up-Regulation

Zymosan was hydrolysed with HCl and fractionated by ultrafiltration and dialysis to obtain water-soluble fragments A, B and C. Physical and chemical analyses showed that these fractions are composed primarily of glucose and have molecular weights of 8 kDa, 5 kDa and 2 kDa, respectively. A glycosidic linkage analysis indicated that they are mainly composed of β-1,3-glucans. Fragment A, which has the highest molecular weight, contains approximately 30% β-1,6-linked glucans, but fragment C is almost entirely composed of linear β-1,3-glucan chains. The anti-chronic atrophic gastritis activity experiments showed that fragment A has significant activity, the activity of zymosan is quite low and the activities of fragments B and C are in between those of fragment A and zymosan.

Topics: Animals; beta-Glucans; Bile; Chromatography, Gel; Chronic Disease; Disease Models, Animal; Gastric Mucosa; Gastritis, Atrophic; Immunization; Inflammation; Molecular Weight; Rats; Rats, Wistar; Swine; Zymosan

1,3-β-Glucan was a major cell wall component of fungus. The existing studies showed that 1,3-β-glucan exposure could induce lung inflammation that involved both Th1 and Th2 cytokines. Regulatory T cells (Treg cells) played a critical role in regulating immune homeostasis by adjusting the Th1/Th2 balance. The role of Treg cells and regulatory mechanism in 1,3-β-glucan-induced lung inflammation is still unclear. In our study, mice were exposed to 1,3-β-glucan by intratracheal instillation. To investigate the role of Treg cells in response to 1,3-β-glucan, we generated Treg-depleted mice by intraperitoneal administration of anti-CD25 mAb. The Treg-depleted mice showed more inflammatory cells and severer pathological inflammatory change in lung tissue. Depletion of Treg cells led to increased Th1 cytokines and decreased Th2 cytokines. Treg-depleted mice showed a decreased expression of anti-inflammation cytokine and lower-level expression of CTLA-4. In all, our study indicated that Treg cells participated in regulating the 1,3-β-glucan-induced lung inflammation. Depletion of Treg cells aggravated the 1,3-β-glucan-induced lung inflammation, regulated the Th1/Th2 balance by enhancing Th1 response. Treg cells exerted their modulation function depending on both direct and indirect mechanism during the 1,3-β-glucan-induced lung inflammation.

Topics: Animals; Antibodies, Monoclonal; beta-Glucans; Bronchoalveolar Lavage; Cytokines; Female; Forkhead Transcription Factors; In Vitro Techniques; Inflammation; Interleukin-2 Receptor alpha Subunit; Lung; Lung Injury; Mice; Mice, Inbred C57BL; T-Lymphocytes, Regulatory; Th1-Th2 Balance

Exposing blood to an artificial surface results in a systemic inflammatory response, including cytokine release and complement activation. We studied the artificial surface-induced inflammation in human whole blood using an extensive panel of inflammatory mediators including proinflammatory cytokines, chemokines and growth-factors and investigated the role of the complement system in the induction of this response. Using multiplex technology, 27 different inflammatory mediators were measured after circulating blood for 4 hours in polyvinyl chloride tubing. The C3 inhibitor compstatin was used to block complement activation. A significant (p < 0.05) increase in 14 of the 27 mediators was induced by the surface, of which 7 were chemokines (IL-8, MCP-1, MIP-1alpha, MIP-1beta, RANTES, eotaxin and IP-10) and 5 were growth-factors (G-CSF, GM-CSF, VEGF, PDGF and FGF). The traditional proinflammatory cytokines like IL-1beta, TNFalpha and IL-6 were not induced, although IL-6, as well as IL-15 and IL-17 increased if the surface was coated with highly bioincompatible laminaran. Inhibition of complement activation with compstatin significantly (p < 0.05) reduced the formation of 12 of the 14 mediators. For 10 of the 12 mediators, the inhibition was by 2/3 or more, for the remaining two the inhibition was more moderate. A highly biocompatible heparin-coated PVC surface was used as negative control and completely abolished the whole inflammatory response. The artificial surface PVC markedly induced a broad spectrum of chemokines and growth-factors, which was largely dependent on activation of complement.

Topics: Anticoagulants; Chemokines; Complement Activation; Complement C3; Cytokines; Glucans; Heparin; Humans; Inflammation; Peptides, Cyclic; Polysaccharides; Polyvinyl Chloride

1-->3-Beta-glucan has been associated with pulmonary inflammation induced by exposure to fungal or yeast cell wall dust. 1-->3-Beta-glucan is the major cell wall component of yeast or fungi. However, the yeast cell wall contains several other components besides 1-->3-beta-glucans, such as mannan and chitin. Few studies evaluated the contribution of these other cell wall components to pulmonary inflammation. The present study compares a crude particulate yeast cell wall preparation (zymosan A) to purified yeast glucan, purified yeast glucan mannan, or purified yeast glucan chitin particles for their potency to induce mouse pulmonary inflammation after in vivo exposure. Mannan is the second most abundant polysaccharide in the yeast cell wall, whereas chitin content is a minor component. The results show that pulmonary injury is mediated by both chitin and 1-->3-beta-glucan and to a lesser degree by mannan. There is also evidence that zymosan is more potent than purified 1-->3-beta-glucan alone. Evidence indicates that 1-->3-beta-glucan is the major inflammatory component in yeast and fungal cell walls.

Topics: Animals; beta-Glucans; Cell Wall; Chitin; Inflammation; Lung; Mice; Yeasts; Zymosan

The acute effects of pure inhaled glucan on respiratory inflammation remain inconclusive and not sufficiently examined with regards to the simultaneous interaction of glucan, endotoxin (lipopolysaccharide, LPS), and house dust in airway inflammation. This study aims at determining effects of simultaneous exposure to office dust and glucan on nasal and pulmonary inflammation. This is relevant for humans with occupational exposure in waste handling and farming and buildings with mold problems. Office dust collected from Danish offices was spiked with 1% (1-3)-beta-glucan (curdlan). Guinea pig nasal cavity volume was measured by acoustic rhinometry (AR) and animals were exposed by inhalation for 4 h to curdlan-spiked dust, unspiked dust, purified air (negative controls), or LPS (positive controls). After exposure (+5 h) or the following day (+18 h), measurements were repeated by AR and followed by bronchoalveolar lavage (BAL). Total and differential cell counts, interleukin (IL)-8 in BAL fluid, and change in nasal volume were compared between groups. A 5-10% increase in nasal volume was seen for all groups including clean air except for a significant 5% decrease for spiked-dust inhalation (+18 h). No marked differences were observed in BAL cells or IL-8 except in LPS-exposed controls. The delayed decrease of nasal cavity volume after exposure to glucan spiked dust suggests a slow effect on the upper airways for curdlan and office dust together, though no pulmonary response or direct signs of inflammation were observed. Glucan-spiked office dust exposures produced a delayed nasal subacute congestion in guinea pigs compared to office dust alone, but extrapolated to nasal congestion in humans, paralleling the nasal congestion seen in human volunteers exposed to the same dust, this may not have clinical importance.

Topics: Air Pollutants; Air Pollution, Indoor; Animals; beta-Glucans; Bronchoalveolar Lavage Fluid; Denmark; Dust; Guinea Pigs; Inflammation; Interleukin-8; Leukocyte Count; Lung; Male; Nasal Cavity; Particle Size; Workplace

Eosinophils are a characteristic component of the inflammatory response seen in several diseases, including allergic asthma and chronic obstructive pulmonary disease. After activation, eosinophil-derived products may exert proinflammatory effects and cause considerable tissue damage. In the present study, we investigated innate interactions between the respiratory tract pathogen nontypeable Haemophilus influenzae (NTHi) and human eosinophils. Bacterial binding to eosinophils was dependent on (1-3)-beta-D-glucan receptors, as deduced from blocking experiments using the soluble glucan derivatives laminarin and scleroglucan. In addition, expression of the beta-glucan receptor dectin-1 was shown in eosinophils by reverse transcriptase-polymerase chain reaction. Activation of the beta-glucan receptors by bacteria elicited a time- and dose-dependent respiratory burst in eosinophils. NTHi caused increased expression of the proinflammatory chemokine interleukin-8 as measured by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. Incubation of eosinophils in the presence of NTHi for 4.5 h revealed upregulation of 245 different genes as detected by microarray. Signal transduction-related transcripts were most strongly upregulated, followed by cytokine mRNAs. Our findings suggest that NTHi can induce an innate inflammatory response in eosinophils that is mainly mediated via beta-glucan receptors. This points to possible pathophysiologic mechanisms involving innate recognition of NTHi by eosinophils during infection of the airways, thus promoting inflammation in chronic pulmonary disease.

Topics: Eosinophils; Gene Expression Profiling; Glucans; Haemophilus influenzae; Humans; Inflammation; Interleukin-8; Polysaccharides; Protein Isoforms; Receptors, Immunologic; Respiratory Burst; RNA, Messenger; Signal Transduction

To evaluate the effect of a microbial cell wall component--(1-->3)-beta-D-glucan--on the inflammatory effect induced by cigarette smoke in a subchronic exposure situation.. Groups of guinea-pigs were exposed 5 days/week to cigarette smoke, an aerosol of (1-->3)-beta-D-glucan, or to both.. The numbers of different inflammatory cells were studied in histological sections, enzyme digested lung tissue and in lung lavage. Cell enzyme production was measured.. Exposure to (1-->3)-beta-D-glucan or cigarette smoke caused only minor alterations in inflammatory cells. Given together they caused an increase in cellularity in the tissue with significantly increased numbers of macrophages, lymphocytes, neutrophils and eosinophils. There was also an increase in subepithelial eosinophils. Lung lavage cell enzyme production was slightly lower in the combined exposure group.. The results demonstrate that (1-->3)-beta-D-glucan synergistically increases the inflammation induced by cigarette smoke. The mechanism may be a downregulation of the macrophage control of inflammatory cell migration into the lung tissue.

Topics: Aerosols; Animals; beta-Glucans; Bronchoalveolar Lavage Fluid; Cell Movement; Female; Glucans; Guinea Pigs; Inflammation; Lung; Lysosomes; Male; Time Factors; Tobacco Smoke Pollution; Trachea

A collagen-impregnated graft, called Hemashield, has been used clinically; however, some complications such as pyrexia, fluid accumulation, and unusual scar formation around the graft have been reported. To understand the cause of these problems, the graft was examined both in vivo and in vitro. Endotoxin and (1-3)beta-D-glucan were detected in the extract from Hemashield by special quantitative methods called Toxicolor and Endospecy. In an animal study, the grafts were implanted in the thoracic descending aorta of 9 dogs and were designed to explant at 2 weeks. Macroscopic evaluation of the explants showed that the graft had no infection, but fluid accumulation was found in the pleural cavity and around the graft-like seroma. Microscopical observations revealed that neither fibroblasts nor capillary blood vessels had infiltrated in the adventitial side of the graft, but numerous plasma cells, lymphocytes, and macrophages were noticed. The impregnated collagen was partially absorbed. These results indicate that the graft had some contaminants which contained a certain amount of endotoxin and (1-3)beta-D-glucan, resulting in noninfective inflammatory responses around the graft.

Topics: Animals; Aorta, Thoracic; beta-Glucans; Blood Vessel Prosthesis; Collagen; Dogs; Endotoxins; Female; Glucans; Inflammation; Male; Pleural Effusion

Effects of murine serum (NMS) treatment on (1-->3)-beta-D-glucan inhibitable uptake of zymosan particles (ZYM) (GIZUP) by murine peritoneal macrophages (PM) and the structural specificity of the inhibition were examined. ZYM uptake by PM treated with NMS was enhanced in comparison with those treated with medium, and in a concentration- and incubation time-dependent manner. The enhanced ZYM uptake was significantly reduced by the pretreatment of PM with soluble (1-->3)-beta-D-glucans. These facts suggest that NMS enhances GIZUP. The effect disappeared by the treatment of NMS with gelatin-Sepharose which removed fibronectin (FN) from the serum, suggesting a significant contribution of FN on GIZUP. In addition, the administration of beta-glucan in vivo elevated the concentration of FN in serum by acute phase response and enhanced GIZUP, suggesting the positive contribution of acute phase responses on beta-glucan mediated immunopharmacological activities. Of particular interest, the inhibition was shown by both antitumor active and inactive glucans. These facts suggested that the recognition of beta-glucans by PM, which would proceed at a relatively early period of whole activation pathways, would not be enough to fully activate the host to show antitumor activity.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Fibronectins; Glucans; In Vitro Techniques; Inflammation; Macrophages; Male; Mice; Mice, Inbred ICR; Peritoneal Cavity; Phagocytosis; Structure-Activity Relationship; Zymosan