Endogenous Glucocorticoid Deficiency in Psoriasis Promotes Inflammation and Abnormal Differentiation

Mrinal K. Sarkar, Nihal Kaplan, Lam C. Tsoi, Xianying Xing, Yun Liang, William R. Swindell, Paul Hoover, Maya Aravind, Gleb Baida, Matthew Clark, John J. Voorhees, Rajan P. Nair, James T. Elder, Irina Budunova, Spiro Getsios, Johann E. Gudjonsson*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

The factors involved in maintaining a localized inflammatory state in psoriatic skin remain poorly understood. Here, we demonstrate through metabolomic and transcriptomic profiling marked suppression of glucocorticoid biosynthesis in the epidermis of psoriatic skin leading to localized deficiency of cortisol. Utilizing a 3D human epidermis model, we demonstrate that glucocorticoid biosynthesis is suppressed by proinflammatory cytokines and that glucocorticoid deficiency promotes inflammatory responses in keratinocytes. Finally, we show in vitro and in vivo that treatment with topical glucocorticoids leads to rapid restoration of glucocorticoid biosynthesis gene expression coincident with normalization of epidermal differentiation and suppression of inflammatory responses. Taken together, our data suggest that localized glucocorticoid deficiency in psoriatic skin interferes with epidermal differentiation and promotes a sustained and localized inflammatory response. This may shed new light on the mechanism of action of topical steroids, and demonstrates the critical role of endogenous steroid in maintaining both inflammatory and differentiation homeostasis in the epidermis.

Original languageEnglish (US)
Pages (from-to)1474-1483
Number of pages10
JournalJournal of Investigative Dermatology
Volume137
Issue number7
DOIs
StatePublished - Jul 2017

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Sarkar, M. K., Kaplan, N., Tsoi, L. C., Xing, X., Liang, Y., Swindell, W. R., Hoover, P., Aravind, M., Baida, G., Clark, M., Voorhees, J. J., Nair, R. P., Elder, J. T., Budunova, I., Getsios, S., & Gudjonsson, J. E. (2017). Endogenous Glucocorticoid Deficiency in Psoriasis Promotes Inflammation and Abnormal Differentiation. Journal of Investigative Dermatology, 137(7), 1474-1483. https://doi.org/10.1016/j.jid.2017.02.972