The Jake Gittlen Cancer Research Foundation and Department of Dermatology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Br J Dermatol. 2011 Sep;165(3):526-33. doi: 10.1111/j.1365-2133.2011.10392.x. Epub 2011 Aug 17.
The full mechanism of action of isotretinoin [13-cis retinoic acid (13-cis RA)] in treating acne is unknown. 13-cis RA induces key genes in sebocytes that are involved in apoptosis, including Tumor necrosis factor Related Apoptosis Inducing Ligand (TRAIL).
In this study, we investigated the role of 13-cis RA-induced TRAIL within SEB-1 sebocytes.
Using 13-cis RA and recombinant human TRAIL (rhTRAIL) protein, we assessed induction of TRAIL and apoptosis in SEB-1 sebocytes, normal keratinocytes and patient skin biopsies.
Treatment with rhTRAIL protein increased TUNEL-positive staining in SEB-1 sebocytes. TRAIL siRNA significantly decreased the percentage of TUNEL-positive SEB-1 sebocytes in response to 13-cis RA treatment. Furthermore, TRAIL expression increased in the skin of patients with acne after 1 week of isotretinoin therapy compared with baseline. TRAIL expression localized within sebaceous glands. Unlike sebocytes, TRAIL protein expression was not increased in normal human epidermal keratinocytes in response to 13-cis RA, nor did rhTRAIL induce apoptosis in keratinocytes, suggesting that TRAIL is key in the sebocyte-specific apoptotic effects of 13-cis RA.
Taken together, our data suggest that TRAIL, like the neutrophil gelatinase-associated lipocalin, is involved in mediating 13-cis RA apoptosis of sebocytes.
异维 A 酸（13-顺式维 A 酸）治疗痤疮的作用机制尚不完全清楚。13-顺式维 A 酸可诱导皮脂腺中涉及细胞凋亡的关键基因，包括肿瘤坏死因子相关凋亡诱导配体（TRAIL）。
本研究旨在探讨 13-顺式维 A 酸诱导的 SEB-1 皮脂腺细胞中 TRAIL 的作用。
采用 13-顺式维 A 酸和重组人 TRAIL（rhTRAIL）蛋白，检测 SEB-1 皮脂腺细胞、正常角质形成细胞和患者皮肤活检标本中 TRAIL 的诱导和凋亡情况。
rhTRAIL 蛋白处理可增加 SEB-1 皮脂腺细胞的 TUNEL 阳性染色。TRAIL siRNA 显著降低了 13-顺式维 A 酸处理后 TUNEL 阳性 SEB-1 皮脂腺细胞的比例。此外，与基线相比，接受异维 A 酸治疗 1 周后，痤疮患者皮肤中 TRAIL 的表达增加。TRAIL 表达定位于皮脂腺内。与皮脂腺不同，13-顺式维 A 酸不能诱导正常人类表皮角质形成细胞中 TRAIL 蛋白的表达，rhTRAIL 也不能诱导角质形成细胞凋亡，提示 TRAIL 是 13-顺式维 A 酸诱导皮脂腺细胞凋亡的关键。
综上所述，我们的数据表明，TRAIL 像中性粒细胞明胶酶相关脂质运载蛋白一样，参与介导 13-顺式维 A 酸对皮脂腺细胞的凋亡作用。
