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
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.
https://doi.org/10.1074/jbc.M110.188268
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Cortisol Chemical Compounds 100%
Steroid 11-beta-Hydroxylase Medicine & Life Sciences 78%
Epidermis Medicine & Life Sciences 77%
Hydrocortisone Medicine & Life Sciences 69%
Wound Healing Medicine & Life Sciences 42%
Glucocorticoid Chemical Compounds 37%
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
Cortisol synthesis in epidermis is induced by IL-1 and tissue injury. / Vukelic, Sasa; Stojadinovic, Olivera; Pastar, Irena et al.
In: Journal of Biological Chemistry, Vol. 286, No. 12, 25.03.2011, p. 10265-10275.
Vukelic, S, Stojadinovic, O, Pastar, I, Rabach, M, Krzyzanowska, A, Lebrun, E, Davis, SC, Resnik, S, Brem, H & Tomic-Canic, M 2011, 'Cortisol synthesis in epidermis is induced by IL-1 and tissue injury', Journal of Biological Chemistry, vol. 286, no. 12, pp. 10265-10275. https://doi.org/10.1074/jbc.M110.188268
Vukelic S, Stojadinovic O, Pastar I, Rabach M, Krzyzanowska A, Lebrun E et al. Cortisol synthesis in epidermis is induced by IL-1 and tissue injury. Journal of Biological Chemistry. 2011 Mar 25;286(12):10265-10275. doi: 10.1074/jbc.M110.188268
Vukelic, Sasa ; Stojadinovic, Olivera ; Pastar, Irena et al. / Cortisol synthesis in epidermis is induced by IL-1 and tissue injury. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 12. pp. 10265-10275.
@article{8a0d8b4697254736a2fac52d0606fe5a,
title = "Cortisol synthesis in epidermis is induced by IL-1 and tissue injury",
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.",
author = "Sasa Vukelic and Olivera Stojadinovic and Irena Pastar and Morgan Rabach and Agata Krzyzanowska and Elizabeth Lebrun and Davis, {Stephen C.} and Sydney Resnik and Harold Brem and Marjana Tomic-Canic",
doi = "10.1074/jbc.M110.188268",
journal = "Journal of Biological Chemistry",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
T1 - Cortisol synthesis in epidermis is induced by IL-1 and tissue injury
AU - Vukelic, Sasa
AU - Stojadinovic, Olivera
AU - Pastar, Irena
AU - Rabach, Morgan
AU - Krzyzanowska, Agata
AU - Lebrun, Elizabeth
AU - Davis, Stephen C.
AU - Resnik, Sydney
AU - Brem, Harold
AU - Tomic-Canic, Marjana
N2 - 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.
AB - 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.
U2 - 10.1074/jbc.M110.188268
DO - 10.1074/jbc.M110.188268
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry