Local Glucocorticoid Activation by 11β-Hydroxysteroid Dehydrogenase 1 in Keratinocytes: The Role in Hapten-Induced Dermatitis.

Abstract

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.

• Authors: Mika Terao, Saori Itoi, Sayaka Matsumura, Lingli Yang, Hiroyuki Murota, Ichiro Katayama
• Journal: The American journal of pathology (Am J Pathol) Vol. 186 Issue 6 Pg. 1499-510 (06 2016) ISSN: 1525-2191 [Electronic] United States
• PMID: 27070821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Glucocorticoids
• Haptens
• 11-beta-Hydroxysteroid Dehydrogenase Type 1

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 1 (metabolism)
• Animals
• Blotting, Western
• Dermatitis, Contact (metabolism)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Fluorescent Antibody Technique
• Glucocorticoids (metabolism)
• Haptens (toxicity)
• Keratinocytes (metabolism)
• Mice
• Mice, Knockout
• Real-Time Polymerase Chain Reaction