PubMed RSS Feed - -Glucocorticoids Promote CCL20 Expression in Keratinocytes

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Br J Dermatol. 2021 Jun 22. doi: 10.1111/bjd.20594. Online ahead of print.

ABSTRACT

Glucocorticoids (GC) are generally envisioned as immunosuppressive, but in conditions such as rosacea and perioral dermatitis they can lead to increased skin inflammation. In lung epithelia, GC promote expression of the pro-inflammatory cytokine CCL20, which contributes to steroid-resistant asthma. In the skin, CCL20 stimulates inflammation by recruiting Th17 T-lymphocytes and dendritic cells and is elevated in papulopustular rosacea. The objective of this study was to understand if and how glucocorticoids affect CCL20 expression in human keratinocytes. CCL20 expression was assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and ELISA. Selective inhibition of candidate genes and signaling pathways was performed using RNA interference and chemical inhibitors. The binding of activated glucocorticoid receptor to genomic DNA was determined by chromatin immunoprecipitation, and enhancer activity of genomic sequences was measured with a reporter assay. We found that GC treatment increased CCL20 expression in human keratinocytes and murine skin, both in the undisturbed state and with tumor necrosis factor-α (TNFα) stimulation. GC repressed pro-inflammatory signaling pathways including NFκB and p38/MAPK, but these inhibitory effects were opposed by the direct binding of activated glucocorticoid receptor to the CCL20 enhancer, promoting CCL20 expression. Viewed together, these findings demonstrate a mechanism by which GC induce expression of CCL20 in keratinocytes, which may contribute to the inflammation seen in steroid-exacerbated skin conditions.

PMID:34157145 | DOI:10.1111/bjd.20594

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