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Cortisol Synthesis in Epidermis Is Induced by IL-1 and Tissue Injury
Open accessAbstract
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. We show 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.
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“Skin also expresses 11βHSD2 which works in the oxidative direction, converting cortisol to the inactive cortisone [23, 64–66, 81].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [65]
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“In contrast, dexamethasone treatment of human skin was reported to increase 11βHSD2 expression at the mRNA level [65].”
From Steroidogenesis in the skin: Implications for local immune functions (2013) · cites this paper as [65]
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“Moreover, cortisol synthesis in the epidermis exhibits a negative feedback effect on inflammatory cytokine IL-1 upon tissue injury (24).”
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“regulators of adaptive immune function, including some cellular and tissue repair mechanisms (Chrousos, 1999; McEwen et al., 1997; Vukelic et al., 2011).”
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“Secretion of growth factors and cytokines including FGFs, EGF, IL-1, and IL-6 stimulates keratinocyte proliferation and migration, a process called re-epithelialization, normally accompanied by collagen deposition, formation of new granulation tissue, and wound contraction [87, 88].”
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“Further examples of creating full-thickness ex vivo wound models by punching are reported in References [75, 77, 80, 84, 86, 89, 98–106].”
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“Conclusions Altogether, our results support the relevance of the epidermal GRmediated signaling, cutaneous steroidogenesis and the production of skin-secreted factors to modulate local and systemic responses [4,15,68].”
Quoi de neuf en recherche dermatologique ?
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“of central hypothalamus-pituitary-adrenal (HPA) axis function [18-20].”
BackgroundDermal glucocorticoids are uncoupled from stress physiology and infection
Quadros, V., Inman, B., McDonnell, N. B., Williams, K., Romero, L. M., & Woodhams, D. C. (2025) · Conservation Physiology · doi:10.1093/conphys/coaf005 · Cited by 2
“Dermal swabbing aims to monitor HPI function; however, clinical research in humans has demonstrated that epidermal cells synthesize their own Pro-opiomelanocortin (POMC), ACTH and Cortisol (Hannen et al. , 2017; Jozic et al. , 2014; Phan et al. , 2021; Vukelic et al. , 2011).”
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“Up-regulation of CYP11B1 and subsequent enhanced production of cortisol was induced by the proinflammatory cytokine IL-1β and depressed by insulin-like growth factor 1 (IGF-1) [19].”
Cortisol Metabolism as a Regulator of the Tissue-Specific Glucocorticoid Action
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Equivalent of Hypothalamo–Pituitary–Adrenal Axis in the Skin
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Sensory Systems of Epidermal Keratinocytes
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Corticotropin Signaling System in the Skin
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BackgroundAnalysis of HSD11B2 as a prognostic marker in Melanoma via TCGA data miningPreprint
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Local Actions of Thyrotropin-Releasing Hormone Regulate Hair Color
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“The skin has recently been found to produce cortisol and thereby serves as an extra-adrenal site of glucocorticoid synthesis, albeit in a tightly regulated manner, to simulate the hypothalamus–pituitary– adrenal axis (Vukelic et al., 2011).”
BackgroundExtraadrenalis glükokortikoidszintézis
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THE MOLECULAR MECHANISM, TYPES AND TREATMENT OF SCAR FORMATION
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Glucocorticoid metabolism and activation
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The Skin–brain Axis in Cutaneous Aging: Neurobiological Foundations and Clinical Implications
Khalaf, A. T., BADER, H., Alkhaffaf, W. H., Zakaria, Y. D. M., Abdullah, O. Y., & Al-Mallah, M. N. S. (2026) · The Open Dermatology Journal · doi:10.2174/0118743722507190261009061047
Metadata
- Authors
- Vukelic, S., Stojadinovic, O., Pastar, I., Rabach, M., Krzyzanowska, A., Lebrun, E., Davis, S. C., Resnik, S., Brem, H., & Tomic-Canic, M.
- Affiliations
- Lenox Hill Hospital (US)
- University of Miami (US)
- SUNY Downstate Health Sciences University (US)
- Hospital for Special Surgery (US)
- NYU Langone Health (US)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 286
- Issue
- 12
- Pages
- 10265-10275
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3060481
- OpenAlex
- W2080660266
- Cited by
- 193
- References
- 67
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 7 · 2023: 6 · 2022: 12 · 2021: 11 · 2020: 18 · 2019: 9 · 2018: 11 · 2017: 18 · 2016: 17 · 2015: 8 · 2014: 15 · 2013: 19 · 2012: 13
- FWCI
- 18.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Nursing Research (R01NR008029, NR008029)
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK090135)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Keywords
- cortisol production, epidermis, keratinocytes, wound healing, IL-1β, tissue damage, CYP11B1, 11β-hydroxysteroid dehydrogenase type 2, glucocorticoid receptor, ACTH, metyrapone, negative feedback regulation, inflammatory cytokines
- MeSH terms
- Adrenocorticotropic Hormone, Animals, Enzyme Inhibitors, Epidermis, Hormones, Humans, Hydrocortisone, Inflammation, Metyrapone, Steroid 11-beta-Hydroxylase, Swine, Wound Healing, Keratinocytes, Interleukin-1beta
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