Funding sources This study was supported by a faculty research grant of Yonsei University College of Medicine for 2011 (6–2011–0144).
CLINICAL AND LABORATORY INVESTIGATIONS
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
Article first published online: 21 DEC 2012
© 2012 The Authors. BJD © 2012 British Association of Dermatologists
British Journal of Dermatology
Volume 168, Issue 1, pages 47–55, January 2013
How to Cite
Lee, S.E., Kim, J.-M., Jeong, M.-K., Zouboulis, C.C. and Lee, S.H. (2013), 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. British Journal of Dermatology, 168: 47–55. doi: 10.1111/bjd.12009
Conflicts of interest None declared.
S.E.L. and J.-M.K. contributed equally to this work.
- Issue published online: 21 DEC 2012
- Article first published online: 21 DEC 2012
- Accepted manuscript online: 16 AUG 2012 12:08PM EST
- Accepted for publication 9 August 2012
Background Glucocorticoids (GCs) affect the pathophysiology of sebaceous glands, causing development or exacerbation of acne. The availability of GCs is regulated by isoenzymes of 11β-hydroxysteroid dehydrogenase (11βHSD) at tissue-specific levels. 11βHSD type 1 (HSD11β1) is a reductase, catalysing the conversion of cortisone to active cortisol, and is highly expressed in liver and adipose tissue. Recently, HSD11β1 was observed in human skin in keratinocytes and fibroblasts.
Objectives To investigate the expression of HSD11β1 in sebaceous glands of normal and acne-involved skin, and to examine the role of HSD11β1 in GC-induced lipid synthesis and toll-like receptor 2 (TLR2) expression in sebocytes.
Methods Expression of HSD11β1 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 HSD11β1 inhibitor and the small interference RNA (siRNA) approach were used to investigate the role of HSD11β1 on the GC regulation of sebocyte functions.
Results HSD11β1 was expressed in human sebaceous glands and upregulated in acne lesional skin. HSD11β1 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 HSD11β1 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 HSD11β1 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.