Over the past decade, extra-adrenal cortisol production was reported in various tissues. The enzyme that catalyzes the conversion of hormonally inactive cortisone into active cortisol in cells is 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). We recently reported that 11β-HSD1 is also expressed in keratinocytes and regulates inflammation and keratinocyte proliferation. To investigate the function of 11β-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte-specific 11β-HSD1 knockout (K5-Hsd11b1-KO) mice and analyzed the inflammatory response in models of hapten-induced contact irritant dermatitis. K5-Hsd11b1-KO mice showed enhanced ear swelling in low-dose oxazolone-, 2,4,6-trinitro-1-chlorobenzene (TNCB)-, and 2,4-dinitrofluorobenzene-induced irritant dermatitis associated with increased inflammatory cell infiltration. Topical application of corticosterone dose dependently suppressed TNCB-induced ear swelling and cytokine expression. Similarly in mouse keratinocytes in vitro, corticosterone dose dependently suppressed 2,4,6-trinitrobenzenesulfonic acid-induced IL-1α and IL-1β expression. The effect of 11-dehydrocorticosterone was attenuated in TNCB-induced irritant dermatitis in K5-Hsd11b1-KO mice compared with wild-type mice. In human samples, 11β-HSD1 expression was decreased in epidermis of psoriasis vulgaris compared with healthy skin. Taken together, these data suggest that corticosterone activation by 11β-HSD1 in keratinocytes suppresses hapten-induced irritant dermatitis through suppression of expression of cytokines, such as IL-1α and IL-1β, in keratinocytes.
& Ichiro Katayama (2015) A vitamin D analog inhibits Th2 cytokine-and TGFβ -induced periostin production in fibroblasts: a potential role for vitamin D in skin sclerosis, Dermato-Endocrinology, 7:1, e1010983, DOI: 10.1080DOI: 10. /19381980.2015 Scleroderma is an autoimmune disease characterized by extracellular matrix deposition and inflammation. Topical vitamin D analogs have been reported as effective treatments for scleroderma. We previously reported that a matricellular protein, periostin (POSTN), contributes to pathogenesis of scleroderma as POSTN knockout mice were resistant to bleomycin (BLM)-induced scleroderma. We investigated whether a vitamin D analog affects the expression of POSTN in dermal fibroblasts and in a BLM-induced scleroderma model. The vitamin D analog, maxacalcitol ), was applied to dermal fibroblasts and POSTN expression was measured. The effect of OCT on Th2 cytokine-and TGFb-induced POTSN and Collagen 1 a 1 (Col1A1) expression was also assessed. In vivo, OCT was administered to BLM-induced scleroderma model and outcomes were determined by dermal thickness, collagen density and POSTN expression. Treatment with OCT significantly decreased POSTN expression in dermal fibroblasts. Th2 cytokine-and TGFb-induced expression of POSTN and Col1A1 was also suppressed by OCT. In vivo, OCT administration decreased the density of collagen bundles and POSTN expression in a BLM-induced scleroderma model. In addition to the previously reported immunosuppressive effect, the vitamin D analog OCT might be effective to treat scleroderma, in part through inhibition of Th2 cytokine-and TGFb-induced POSTN expression.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.