Cortistatin is dysregulated in skin tissue of patients with psoriasis vulgaris and suppresses keratinocyte proliferation in vitro.

BACKGROUND: Psoriasis is characterized by the unregulated proliferation of epidermal keratinocytes and increased expression of proinflammatory mediators in the skin. Cortistatin, an endogenous cyclic neuropeptide, inhibits the proliferation of inflammatory cells. We investigated the expression of cortistatin in patients with psoriasis vulgaris and examined its effects on keratinocyte growth in vitro. METHODS: Serum levels of cortistatin were determined by enzyme-linked immunosorbent assay (ELISA) in 72 patients with psoriasis vulgaris and 76 age-matched healthy volunteers. Cortistatin expression was also examined by immunohistochemistry of skin biopsies from 14 patients and 14 healthy subjects. The effects of cortistatin on the proliferation of primary keratinocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and BrdU incorporation assay. Intracellular levels of cAMP in keratinocytes in the presence or absence of cortistatin were determined by ELISA. RESULTS: Serum levels of cortistatin and expression levels in skin were significantly lower in patients with psoriasis than in healthy subjects. Cortistatin inhibited keratinocyte proliferation in vitro in a dose-dependent manner and substantially reduced intracellular cAMP levels in keratinocytes. CONCLUSIONS: Cortistatin is downregulated in the skin of patients with psoriasis vulgaris and suppresses keratinocyte growth in vitro.

The role of CGRP and CALCA T-692C single-nucleotide polymorphism in psoriasis vulgaris.

Calcitonin gene related protein (CGRP) is increased in both lesional and non-lesional psoriasis. The role of CGRP in the pathogenesis of psoriasis vulgaris is still not clear. We designed to determine the CGRP-I (or CALCA), II (or CALCB) gene expression and morbidity and CALCA T-692C single-nucleotide polymorphism (SNP). Peripheral blood mononuclear cells (PBMCs) and plasma samples were collected, and CGRP level and CGRP-I, II mRNA expression were measured in psoriasis patients and healthy controls. The CALCA T-692C genetic polymorphism in psoriasis and control subjects was also compared. A higher expression of CGRP-I, II mRNA in PBMCs in psoriasis patients. The plasma CGRP level in psoriasis patients was also higher than that in healthy subjects. SNP analysis showed carriers of the T-692C allele were over-represented in non-drinking Patients. The plasma CGRP level was higher in alcohol-drinking patients with TT genotype than that with TC genotype. The plasma CGRP level is increased in psoriasis patients and CALCA T-692C polymorphism TT genotype is a factor for the affectability in alcohol-drinking Psoriasis vulgaris patients.