elafin and Psoriasis

Psoriasis is a pathological condition characterized by immune system dysfunction and inflammation. Patients with psoriasis are more likely to develop a wide range of disorders associated with inflammation. Serum levels of various substances and their combinations have been associated with the presence of the disease (psoriasis) and have shown the potential to reflect its activity. The aim of the present study is to contribute to the elucidation of pathophysiological links between psoriasis, its pro-inflammatory comorbidity metabolic syndrome (MetS), and the expression of clusterin and elafin, which are reflected in the pathophysiological "portfolio" of both diseases.. Clinical examinations (PASI score), ELISA (clusterin, elafin), and biochemical analyses (parameters of MetS) were performed.. We found that patients with psoriasis were more often afflicted by MetS, compared to the healthy controls. Clusterin and elafin levels were higher in the patients than in the controls but did not correlate to the severity of psoriasis.. Our data suggest that patients with psoriasis are more susceptible to developing other systemic inflammatory diseases, such as MetS. The levels of clusterin and elafin, which are tightly linked to inflammation, were significantly increased in the patients, compared to the controls, but the presence of MetS in patients did not further increase these levels.

Topics: Adult; Body Mass Index; Case-Control Studies; Clusterin; Comorbidity; Elafin; Female; Gene Expression Regulation; Humans; Inflammation; Male; Metabolic Syndrome; Middle Aged; Psoriasis; Severity of Illness Index

Psoriasis is a distressing chronic skin disease. Its exact pathogenesis is still unclear, as many factors interplay in its occurrence.. The aim of the study is to estimate elafin levels in the serum of both cases and controls and to correlate the levels with psoriasis severity and other markers of inflammation.. Twenty-six psoriatic cases along with 26 healthy controls were assigned in this case-control study. Psoriasis severity was determined by Psoriasis Area and Severity Index score. Elafin levels were measured by ELISA in serum of both cases and controls. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in the cases.. Elafin levels show highly statistical significance difference (P < 0.001) between cases and controls. There is a statistical significant correlation between elafin levels and both psoriasis severity and inflammation markers as CRP and ESR.. Elafin represents a mirror for psoriasis severity and inflammatory state.

Topics: Adolescent; Adult; Aged; Biomarkers; Blood Sedimentation; C-Reactive Protein; Case-Control Studies; Child; Elafin; Female; Humans; Inflammation; Male; Middle Aged; Psoriasis; Severity of Illness Index; Young Adult

Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum.

Topics: Adult; Biomarkers; Blood Proteins; Case-Control Studies; Chemokine CCL22; Drugs, Chinese Herbal; Elafin; Female; Gene Expression; Humans; Interleukin-12 Subunit p40; Male; Mass Spectrometry; Medicine, Chinese Traditional; Metabolic Networks and Pathways; Middle Aged; Principal Component Analysis; Protein Array Analysis; Proteome; Proteomics; Psoriasis; Severity of Illness Index

Previous research revealed heterogeneity in the perfusion intensity within clinically homogenous-appearing plaques, without differences in erythema. In addition, an increased perfusion was found within the perilesional skin. This raises the question whether the heterogeneity in perfusion found both inside and outside a lesion influences the expression levels of genes and proteins involved in the pathogenesis of psoriasis.. To correlate the perfusion intensity to mRNA and protein expression of genes associated with the pathogenesis of psoriasis and to visualize the dynamics of the perfusion intensity over time using laser Doppler perfusion imaging.. Fourteen patients with plaque psoriasis were included. The superficial microcirculation and clinical local scores (single usability metric, SUM, scores) were analysed in one representative lesion every 2 weeks. After 8 weeks 4 biopsies were taken, one from a highly perfused area (hotspot) and one from a low perfusion area (coldspot) of the lesional skin, one biopsy from the highly perfused perilesional skin and one from the distant uninvolved skin.. Statistically significant differences in mRNA and protein expression, including IL-17 and TBX21/T-Bet, were found between hotspots and coldspots, and between the highly perfused perilesional and the uninvolved skin. Hotspots tend to remain on the same location during 8 weeks of follow-up.. Within homogenous-appearing psoriatic plaques, there are remarkable differences in mRNA and protein levels, which are correlated with the perfusion intensity and can be detected by using laser Doppler perfusion imaging. In addition, differences in mRNA and protein expression between the highly perfused perilesional skin and the uninvolved skin were found, indicating that several biological changes occur well before clinical changes become manifest.

Topics: Adult; Aged; beta-Defensins; CD3 Complex; Elafin; Female; Gene Expression; Humans; Interleukin-17; Interleukin-8; Keratin-16; Male; Microcirculation; Middle Aged; Platelet Endothelial Cell Adhesion Molecule-1; Psoriasis; RNA, Messenger; Skin; T-Box Domain Proteins

Picea mariana ((Miller) Britton, Sterns, and Poggenburg; Pinaceae) bark has been traditionally used by North American natives for treating topical inflammations. It has been also suggested to improve various inflammatory skin disorders like Psoriasis vulgaris. Extracts from this bark storage protein contain polyphenolic compounds which have well-known antiinflammatory activities. Based on the capacity of polyphenolic compounds to modulate functions of normal human keratinocytes, this study was set up to decipher the mechanisms of action of a chemically characterized polyphenolic extract from Picea mariana bark (BS-EAcf) on lesional keratinocytes of skin with psoriasis vulgaris, a disease driven by the immune system in which TNF-α plays a significant role.. BS-EAcf corresponds to the ethyl acetate soluble fraction from the hot water extract of Picea mariana bark. BS-EAcf effects were evaluated in normal human (NHK) and psoriatic (PK) keratinocytes stimulated by TNF-α. Cell viability was assessed by lactate deshydrogenase release and propidium iodide (PI) staining. The mechanisms of action of BS-EAcf in keratinocytes were investigated by flow cytometry, ELISAs, RT-PCR and western blot analyses.. PK exhibited a higher response to TNF-α than NHK regarding the ICAM-1 expression and the production of NO, IL-6, IL-8, fractalkine and PGE2, whereas BS-EAcf significantly inhibited this TNF-α-induced increase at concentrations without causing keratinocyte toxicity. Additionally, this extract significantly inhibited the TNF-α-induced release of elafin and VEGF by PK and NHK. Since TNF-α activation of most of these factors is dependent on the NF-κB pathway, this latter was studied in TNF-α-activated PK. BS-EAcf inhibited the TNF-α-induced phosphorylation and degradation of total IκBα as well as phosphorylation of NF-κB p65.. The ethyl acetate fraction from Picea mariana bark extract showed inhibitory effects of cytokines, chemokines, adhesion molecules, nitric oxide and prostaglandins produced by keratinocytes under TNF-α activation through down-regulating the NF-κB pathway. This study demontrated that this extract could be a potential antiinflammatory agent capable of improving psoriatic skin.

Topics: Cell Survival; Cells, Cultured; Elafin; Gene Expression Regulation; Humans; Intercellular Adhesion Molecule-1; Keratinocytes; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Picea; Plant Bark; Plant Extracts; Psoriasis; Tumor Necrosis Factor-alpha

Psoriasis is a complex inflammatory skin disease that presents a wide variety of clinical manifestations. Human β defensin-2 (hBD-2) is highly up-regulated in psoriatic lesions and has been defined as a biomarker for disease activity. We explored the potential benefits of targeting hBD-2 by topical application of DEFB4-siRNA-containing SECosomes in a bioengineered skin-humanized mouse model for psoriasis. A significant improvement in the psoriatic phenotype was observed by histological examination, with a normalization of the skin architecture and a reduction in the number and size of blood vessels in the dermal compartment. Treatment leads to the recovery of transglutaminase activity, filaggrin expression and stratum corneum appearance to the levels similar to those found in normal regenerated human skin. The availability of a reliable skin-humanized mouse model for psoriasis in conjunction with the use of the SECosome technology may provide a valuable preclinical tool for identifying potential therapeutic targets for this disease.

Topics: Administration, Cutaneous; Animals; beta-Defensins; Bioengineering; Cell Differentiation; Cell Proliferation; Dermis; Disease Models, Animal; Elafin; Epidermis; Filaggrin Proteins; Gene Expression; Gene Silencing; Humans; Intermediate Filament Proteins; Keratin-1; Keratin-17; Ki-67 Antigen; Leukocyte L1 Antigen Complex; Liposomes; Mice; Molecular Targeted Therapy; Nanoparticles; Protein Precursors; Psoriasis; RNA, Small Interfering; S100 Calcium Binding Protein A7; S100 Proteins

The exact mechanisms of action of balneophototherapy are incompletely understood. We aimed to investigate the effect of salt water soaks on ultraviolet (UV) transmission and the expression of molecular parameters of psoriasis.. We studied UV transmission and the expression of antimicrobial peptides and skin-derived antileukoproteinase (SKALP/elafin) in psoriatic epidermis equivalents which were pretreated with tap water and differently concentrated salt water solutions. Moreover, we performed in vivo phototoxicity tests in healthy subjects.. Highly concentrated salt water soaks significantly increase UV transmission through psoriatic epidermis equivalents, in particular within the wavelength range of 305- 360 nm. In vivo tests revealed increased photosensitivity following highly concentrated salt water baths. A significant decrease in human β-defensin-2 (hBD-2) and SKALP/elafin is observed after highly concentrated NaCl soaks.. An increase in UV transmission following highly concentrated salt water soaks likely causes enhanced UV gain within the viable epidermis. Moreover, our data indicate that salt water soaks seem to influence the protein profiles of hBD-2 and SKALP/elafin.

Topics: Antimicrobial Cationic Peptides; Balneology; Elafin; Humans; Psoriasis; Skin; Sodium Chloride; Tissue Culture Techniques; Ultraviolet Rays

Avarol, a marine sesquiterpenoid hydroquinone, and 14 avarol derivatives have shown interesting anti-inflammatory properties in previous studies. In this study, avarol and derivatives were evaluated in high-throughput keratinocyte culture models using cytokeratin 10 and SKALP/Elafin expression as markers for respectively normal and psoriatic differentiation. Avarol and five of its derivatives (5, 10, 13, 14 and 15) were selected for further study. Only 10, 13, 14 and 15 were able to inhibit keratinocyte cell growth. Changes in expression levels of 22 genes were assessed by quantitative real time PCR (qPCR). From these genes, TNFalpha mRNA levels showed the strongest changes. For compound 13, 15 and dithranol (used as a model antipsoriatic drug), a dose-dependent downregulation of TNFalpha mRNA was found. The changes in TNFalpha mRNA were confirmed at the protein level for compound 13. Additionally, this compound was able to reduce also IL-8 and COX-2 mRNA levels and this effect was correlated with a reduction in COX-2 protein expression. The mechanism of action of this compound involves at least the inhibition of NF-kappaB-DNA binding activity. In conclusion, our high-throughput screening models in combination with quantitative assessment of changes in gene expression profiles identified the avarol derivative 13, a benzylamine derivative of avarol at the 4' position of benzoquinone ring, as an interesting anti-psoriatic drug candidate that inhibits keratinocyte cell growth and TNFalpha and COX-2 expression.

Topics: Animals; Antineoplastic Agents; Cell Differentiation; Cell Proliferation; Cells, Cultured; Cyclooxygenase 2; Drug Evaluation, Preclinical; Dysidea; Elafin; Enzyme-Linked Immunosorbent Assay; Humans; In Vitro Techniques; Interleukin-8; Keratinocytes; Keratins; Membrane Proteins; Psoriasis; RNA, Messenger; Sesquiterpenes; Tumor Necrosis Factor-alpha