TLR3 augments glucocorticoid-synthetic enzymes expression in epidermal keratinocytes; Implications of glucocorticoid metabolism in rosacea epidermis.

Ryoko Shimada-Omori, Kenshi Yamasaki, Saaya Koike, Takeshi Yamauchi, Setsuya Aiba

Journal of dermatological science 2020 Oct

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While most skin diseases benefit from topical steroids, rosacea symptoms are exacerbated by topical steroids. In the rosacea pathogenesis, abnormal innate immune mechanisms including overexpression of the Toll-like receptor (TLR) have been proposed. However, the links between glucocorticoid metabolism and innate immunity in the epidermis have not been elucidated. In order to understand the pathology by which rosacea symptoms are exacerbated by steroids and environment stimuli, we examined the molecular links between the innate immune system and glucocorticoid synthesis in epidermis. We examined the expression of glucocorticoid-synthetic enzymes in rosacea skin. We stimulated epidermal keratinocytes by TLR ligands and examined the regulation of glucocorticoid-synthetic enzymes. We also employed siRNA and adenovirus vectors to knockdown and transduce TLR molecules, respectively. Rosacea epidermis showed high HSD11B1 in the granular layer. Among TLR ligands, TLR3 ligand Poly(I:C) enhanced the expression of multiple glucocorticoid-synthetic enzymes including HSD11B1 and CYP11A1, and increased cortisol in the cultured media. Induction of HSD11B1 by Poly(I:C) was abolished by pretreatment with TLR3 siRNA. Transfection with an adenoviral vector incorporating TLR3 enhanced HSD11B1 and CYP11A1 protein expression by Poly(I:C). In addition, cell staining revealed increased expression of HSD11B1 and CYP11A1 proteins in the group transfected with TLR3 under the same conditions. TLR3-stimulated epidermal keratinocytes and rosacea epidermis enhance the expression of glucocorticoid-synthetic enzymes, which would promote cortisol activation in the epidermis. The innate immunity modulates glucocorticoid-synthetic enzymes expression via the TLR3 pathway in epidermal keratinocytes. Copyright © 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Citation

Ryoko Shimada-Omori, Kenshi Yamasaki, Saaya Koike, Takeshi Yamauchi, Setsuya Aiba. TLR3 augments glucocorticoid-synthetic enzymes expression in epidermal keratinocytes; Implications of glucocorticoid metabolism in rosacea epidermis. Journal of dermatological science. 2020 Oct;100(1):58-66