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.
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.
Authors: Polina Pyatilova; Tameem Ashry; Yanyan Luo; Jiajun He; Hanna Bonnekoh; Qingqing Jiao; Sherezade Moñino-Romero; Man Hu; Jörg Scheffel; Stefan Frischbutter; Maud A W Hermans; Bradford A Youngblood; Marcus Maurer; Frank Siebenhaar; Pavel Kolkhir Journal: Front Immunol Date: 2022-07-26 Impact factor: 8.786