11β-羟类固醇脱氢酶 1 型在人皮脂腺中表达，并调节 SZ95 皮脂细胞中糖皮质激素诱导的脂质合成和 Toll 样受体 2 表达。
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.
机构信息
Department of Dermatology, CHA Bundang Medical Center, CHA University, 351, Yatap-dong, Bundang-gu, Seongnam 463-712, Korea.
出版信息
Br J Dermatol. 2013 Jan;168(1):47-55. doi: 10.1111/bjd.12009.
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.
背景
糖皮质激素（GCs）影响皮脂腺的病理生理学，导致痤疮的发展或恶化。GC 的可用性受组织特异性水平的 11β-羟类固醇脱氢酶（11βHSD）同工酶调节。11βHSD 类型 1（HSD11β1）是一种还原酶，催化可的松向活性皮质醇的转化，在肝脏和脂肪组织中高度表达。最近，在角质形成细胞和成纤维细胞中观察到人类皮肤中的 HSD11β1。
目的
研究正常和痤疮相关皮肤的皮脂腺中 HSD11β1 的表达，并研究 HSD11β1 在 GC 诱导的脂质合成和皮脂细胞中 toll 样受体 2（TLR2）表达中的作用。
方法
通过免疫组织化学法检测痤疮皮损皮肤和健康志愿者正常皮肤中 HSD11β1 的表达。用地塞米松处理培养的 SZ95 皮脂腺细胞，测定脂质合成和固醇调节元件结合蛋白 1（SREBP-1）和 TLR2 的 mRNA 水平。使用 HSD11β1 抑制剂和小干扰 RNA（siRNA）方法研究 HSD11β1 在 GC 调节皮脂细胞功能中的作用。
结果
HSD11β1 在人皮脂腺中表达，并在痤疮皮损皮肤中上调。HSD11β1mRNA 被地塞米松和 SZ95 皮脂腺细胞中的细胞因子增强。地塞米松通过转录诱导 SREBP-1 部分增强脂质合成，并通过增加 TLR2 mRNA 水平增强脂质合成。PF-915275 或 siRNA 抑制 HSD11β1 可显著抑制 GC 诱导的脂质合成以及 SREBP-1 和 TLR2 的 mRNA 表达。
结论
我们的结果表明，HSD11β1 在调节 GC 对皮脂腺的作用中起关键作用，包括皮脂生成和 TLR2 介导的炎症，从而影响痤疮的发病机制。
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