Cortisol synthesis in epidermis is induced by IL-1 and tissue injury

Sasa Vukelic, Olivera Stojadinovic, Irena Pastar, Morgan Rabach, Agata Krzyzanowska, Elizabeth Lebrun, Stephen C. Davis, Sydney Resnik, Harold Brem, Marjana Tomic-Canic

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

Glucocorticoids (GCs) are known inhibitors of wound healing. In this study we report the novel finding that both keratinocytes in vitro and epidermis in vivo synthesize cortisol and how this synthesis regulates wound healing.Weshow that epidermis expresses enzymes essential for cortisol synthesis, including steroid 11 β-hydroxylase (CYP11B1), and an enzyme that controls negative feedback mechanism, 11β-hydroxysteroid dehydrogenase 2 (11βHSD2). We also found that cortisol synthesis in keratinocytes and skin can be stimulated by ACTH and inhibited by metyrapone (CYP11B1 enzyme inhibitor). Interestingly, IL-1β, the first epidermal signal of tissue injury, induces the expression of CYP11B1 and increases cortisol production by keratinocytes. Additionally, we found induction of CYP11B1 increased production of cortisol and activation of GR pathway during wound healing ex vivo and in vivo using human and porcine wound models, respectively. Conversely, inhibition of cortisol synthesis during wound healing increases IL-1β production, suggesting that cortisol synthesis in epidermis may serve as a local negative feedback to proinflammatory cytokines. Local GCs synthesis, therefore, may provide control of the initial proinflammatory response, preventing excessive inflammation upon tissue injury. Inhibition of GC synthesis accelerated wound closure in vivo, providing the evidence that modulation of cortisol synthesis in epidermis may be an important regulatory mechanism during wound healing.

Original languageEnglish (US)
Pages (from-to)10265-10275
Number of pages11
JournalJournal of Biological Chemistry
Volume286
Issue number12
DOIs
StatePublished - Mar 25 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Vukelic, S., Stojadinovic, O., Pastar, I., Rabach, M., Krzyzanowska, A., Lebrun, E., Davis, S. C., Resnik, S., Brem, H., & Tomic-Canic, M. (2011). Cortisol synthesis in epidermis is induced by IL-1 and tissue injury. Journal of Biological Chemistry, 286(12), 10265-10275. https://doi.org/10.1074/jbc.M110.188268