| First Author | Terao M | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 6 | Pages | 1499-510 |
| PubMed ID | 27070821 | Mgi Jnum | J:233701 |
| Mgi Id | MGI:5787873 | Doi | 10.1016/j.ajpath.2016.01.014 |
| Citation | Terao M, et al. (2016) Local Glucocorticoid Activation by 11beta-Hydroxysteroid Dehydrogenase 1 in Keratinocytes: The Role in Hapten-Induced Dermatitis. Am J Pathol 186(6):1499-510 |
| abstractText | 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 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1). We recently reported that 11beta-HSD1 is also expressed in keratinocytes and regulates inflammation and keratinocyte proliferation. To investigate the function of 11beta-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte-specific 11beta-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-1alpha and IL-1beta 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, 11beta-HSD1 expression was decreased in epidermis of psoriasis vulgaris compared with healthy skin. Taken together, these data suggest that corticosterone activation by 11beta-HSD1 in keratinocytes suppresses hapten-induced irritant dermatitis through suppression of expression of cytokines, such as IL-1alpha and IL-1beta, in keratinocytes. |
