11β-hydroxysteroid dehydrogenase type 1 is expressed in human sebaceous glands and regulates glucocorticoid-induced lipid synthesis and toll-like receptor 2 expression in SZ95 sebocytes

Background Glucocorticoids (GCs) affect the pathophysiology of sebaceous glands, causing development or exacerbation of acne. The availability of GCs is regulated by isoenzymes of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) at tissue-specific levels. 11 beta HSD type 1 (HSD11 beta 1) is a reductase, catalysing the conversion of cortisone to active cortisol, and is highly expressed in liver and adipose tissue. Recently, HSD11 beta 1 was observed in human skin in keratinocytes and fibroblasts. Objectives To investigate the expression of HSD11 beta 1 in sebaceous glands of normal and acne-involved skin, and to examine the role of HSD11 beta 1 in GC-induced lipid synthesis and toll-like receptor 2 (TLR2) expression in sebocytes. Methods Expression of HSD11 beta 1 was examined by immunohistochemistry in acne lesional skin and normal skin of healthy volunteers. The cultured SZ95 sebocytes were treated with dexamethasone, and the lipid synthesis and mRNA levels of sterol regulatory element binding protein 1 (SREBP-1) and TLR2 were determined. Use of an HSD11 beta 1 inhibitor and the small interference RNA (siRNA) approach were used to investigate the role of HSD11 beta 1 on the GC regulation of sebocyte functions. Results HSD11 beta 1 was expressed in human sebaceous glands and upregulated in acne lesional skin. HSD11 beta 1 mRNA was enhanced by dexamethasone and cytokines in SZ95 sebocytes. Dexamethasone enhanced lipid synthesis, partially through the transcriptional induction of SREBP-1, and also by increasing TLR2 mRNA levels. Inhibition of HSD11 beta 1 by PF 915275 or siRNA significantly inhibited the GC-induced lipid synthesis and the mRNA expression of SREBP-1 and TLR2. Conclusions Our results indicate that HSD11 beta 1 plays a key role in the modulation of GC action on sebocytes, including sebum production and TLR2-mediated inflammation, thereby influencing the pathogenesis of acne.