Keratinocytes synthesize and activate cortisol

N Cirillo

Research output: Contribution to journalArticle (Academic Journal)peer-review

69 Citations (Scopus)

Abstract

The bioavailability of circulating and/or endogenous hydrocortisone (cortisol) in epidermal cells is a key determinant in inflammatory disease and chronic wounds. It is not known, however, whether epidermal cells can regulate tissue cortisol and whether they are capable of producing endogenous glucocorticoids. In the present study, we show by microarray analysis that epidermal cells express mRNAs to all the major enzymes involved in the metabolic chain from cholesterol to cortisol, including cytocrome P450, 11-hydroxysteroid dehydrogenases (HSD11Bs), ACTH and GR receptors. The two enzymes mediating activation/deactivation of cortisone to cortisol, namely HSD11B1 and HSD11B2, were expressed at the protein level in oral and skin keratinocytes, in human skin samples as well as in malignant keratinocytes, as shown by Western blotting and immunohistochemistry, respectively. In functional assays, we show that keratinocytes are not only able to activate cortisone to cortisol in a HSD11B-dependent manner but, also, silencing of either HSD11B1 or HSD11B2 specifically modulates the bioavailability of the inactive glucocorticoid and the active steroid, respectively. A further key observation was that keratinocytes responded to stimulation with ACTH by a significant increase in the de novo synthesis of cortisol. Taken together, we provide evidence for a novel non-adrenal steroideal system in human keratinocytes.
Translated title of the contributionKeratinocytes synthesize and activate cortisol
Original languageEnglish
Pages (from-to)1499 - 1505
Number of pages7
JournalJournal of Cellular Biochemistry
Volume112(6)
DOIs
Publication statusPublished - Jun 2011

Bibliographical note

Author of Publication Reviewed: Nicola Cirillo, Stephen S. Prime
Other: IF = 4.586

Fingerprint Dive into the research topics of 'Keratinocytes synthesize and activate cortisol'. Together they form a unique fingerprint.

Cite this