402 Abnormal glucocorticoid synthesis in the lesional skin of erythematotelangiectatic rosacea

Abstract

Rosacea is a chronic inflammatory disorder usually affecting the central face. Chronic use of topical steroids on the face causes lesions similar to rosacea. Synthesis and function of glucocorticoid (GC) have been established in healthy skin and various cutaneous diseases but not in rosacea. In most skin disorders, increased inflammation is usually coupled with a decline in the production of cutaneous GC. We designed this study to investigate the de novo GC synthesis in the skin and GC receptor expression in the lesional and the nonlesional skin of patients with erythematotelangiectatic rosacea (ETR). The key steroidogenic enzymes, 11βHSD1, CYP11A1, 3βHSD2 and CYP21A2, were increased in the lesional skin at the gene and protein levels. CYP17A1 and steroidogenic acute regulatory protein (StAR) tended to be higher in the lesional skin. GC receptor was also significantly increased in the lesional skin. Simultaneously, p65/p50 subunits of nuclear factor kappa-light-chain enhancer of activated B cells (NF-κb) and matrix metalloproteinases (MMP) gene expressions were significantly increased in the lesional skin. These concurrent increments demonstrate that crosstalk between GC receptor and NF-κb may be hampered in the lesional skin of ETR and may contribute to rosacea pathogenesis. We demonstrate that ETR is an inherently inflammatory disorder mediated by NF-κb and that lesional GC synthesis and GC receptor expression is increased in ETR unlike in other cutaneous inflammatory diseases.