The corticotrophin-releasing hormone-proopiomelanocortin (CRH-POMC) system in the skin coordinates pigmentation and the immune response. The aim of this study was to evaluate the regulatory role of the neuroendocrine system in the pathogenesis of psoriasis. Using quantitative real-time-PCR, mRNA expression levels of 15 genes related to the CRH-POMC system were measured in punch biopsies from lesional and non-lesional skin of patients with psoriasis and from skin of healthy control subjects. Statistically significant up-regulation of POMC, CRH receptor type 1, melanin-concentrating hormone receptor (MCHR1) and melanocortin receptors 2, 3 and 4 mRNA expression in lesional and in non-lesional skin compared with healthy control samples were established. Tyrosinase (TYR), T(Y)RP-1 and ASIP genes were statistically significantly down-regulated in lesional and non-lesional skin of psoriasis samples compared with healthy subjects. The up-regulation of POMC, melanocortin receptors, CRH receptor type 1 and MCHR1 in the lesional and non-lesional skin of psoriasis patients supports the importance of the local CRH-POMC system in the pathogenesis of psoriasis.

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Background: Dopamine has been proven to be toxic for melanocytes. In vitiligo patients the level of dopamine is increased and the functioning of several enzymes participating in the dopamine pathway is changed. Methods: With the use of quantitative real-time polymerase chain reaction and ELISA the expression of genes connected to the dopamine pathway (PAH, PCD, TH, DDC, DBH, PNMT, GPX1, MAOA, MAOB, COMT, DRD1–DRD5, VMAT1 and VMAT2) was observed in vitiligo patients’ and control subjects’ skin and blood. Results: The mRNA expression of GPX1, DDC, MAOA, DRD1 and DRD5 differs in vitiligo skin and the protein level of DDC, MAOA, MAOB, DRD1 and DRD5 is changed in vitiligo patients’ skin and/or blood sera. Conclusions: The dopamine pathway probably influences melanogenesis directly or through the melanocortin pathway. We provide new data about changes of expression profile of the dopamine-synthesizing enzyme DDC, the dopamine-degrading enzymes MAOA and MAOB and the D1-like family dopamine receptors in vitiligo skin and blood sera.

BackgroundPlaque psoriasis is a non-contagious skin disease in which characteristic red and flaky lesions result from a dysregulation involving both innate and adaptive immune mechanisms. Several cytokines have been implicated in these processes and lately interleukin (IL)-36 family members have become more recognised among them. Thus far, genetic studies have only investigated IL36RN gene of this family in relation to pustular psoriasis. Since IL36G has previously demonstrated markedly increased levels in plaque psoriasis patients and is linked to IL-23/IL-17 axis critical in psoriasis pathology, it was chosen to be the focus of current report.MethodsEleven SNPs from IL36G region were genotyped in 728 plaque psoriasis patients and 320 healthy control individuals. Allele and haplotype frequencies between patients and controls were assessed by respective association tests. For more specific analyses, the patients were assigned into subgroups according to sex, age of disease onset, occurrence of psoriasis among relatives, seasonal aggravation, arthritis symptoms, body surface area (BSA) scores, and Psoriasis Area and Severity Index (PASI) scores.ResultsThe most significant results were obtained with SNPs rs28947206, rs28947207 and rs28947211 that were associated in entire plaque psoriasis analysis (multiple testing adjusted p value (padj) = 0.0054, padj = 0.0017 and padj = 0.0001) and also several subgroups. The first two of those SNPs were included in the same haplotype block with rs28947205 and rs12328178, and two of the respective haplotypes, CAGC and TGTT, provided similarly significant associations (padj = 0.0462 and padj = 0.0047).ConclusionsThe associated SNPs of this study or those in linkage disequilibrium with them could potentially affect the functionality of IL-36γ cytokine, which in turn may impact plaque psoriasis pathology. For instance, these variants could influence IL-36γ expression or 3D structure, thereby altering its ability to induce chemokine production in keratinocytes and various immune cells. The precise mechanisms of these actions are currently unknown and out of the scope of this study. To conclude, the present genetic association results confirm the proposed role of IL-36γ in plaque psoriasis development, with corresponding causal effects to be determined in forthcoming research.

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