Department of Dermatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China.
Department of Immunology and Microbiology, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China.
Eur J Dermatol. 2021 Feb 1;31(1):32-40. doi: 10.1684/ejd.2021.3964.
Acne vulgaris is a common pilosebaceous disease associated with Propionibacterium acnes (P. acnes). Resolution of comedones may occur in association with shrunken sebaceous glands (SGs) containing de-differentiated cells, however the role of P. acnes is unclear.
To investigate the effects of P. acnes on aryl hydrocarbon receptor (AhR) activation, lipogenesis and differentiation in cultured immortalized human SZ95 sebocytes.
MATERIALS & METHODS: Cultured sebocytes were incubated with formalin-killed (f-) P. acnes (f-P. acnes) at different ratios of multiplicity of infection. The mRNA levels of the AhR downstream cytochrome P450 (CYP) genes were measured by quantitative RT-PCR, nuclear translocation of AhR by western blot and immunofluorescence, lipogenesis and keratinization by gene set enrichment analysis (GSEA), lipid related analysis by Oil red O staining and Nile red staining, and sebaceous differentiation-related gene expression by western blot.
f-P. acnes upregulated CYPs mRNA levels and induced translocation of AhR protein from the cytoplasm into the nucleus. GSEA revealed downregulation of lipogenesis and upregulation of keratinization. f-P. acnes inhibited linoleic acid-induced neutral lipid synthesis and expression of sebocyte markers, keratin 7 and mucin1/EMA, but increased expression of keratinocyte markers, keratin 10 and involucrin, which were abolished by AhR gene silencing. Inhibition of lipogenesis-related genes, such as sterol response element-binding protein, was also observed.
f-P. acnes inhibits lipogenesis and induces terminal differentiation of sebocytes, into keratinocyte-like cells, via activation of the AhR pathway in vitro, suggesting that follicular P. acnes is not only acnegenic but also promotes acne remission through feedback regulation of sebum production.
寻常痤疮是一种常见的皮脂腺疾病，与痤疮丙酸杆菌（P. acnes）有关。粉刺的消退可能与含有去分化细胞的缩小皮脂腺（SG）有关，但 P. acnes 的作用尚不清楚。
研究痤疮丙酸杆菌对永生化人 SZ95 皮脂腺细胞芳香烃受体（AhR）激活、脂肪生成和分化的影响。
培养的皮脂腺细胞用甲醛灭活（f-）痤疮丙酸杆菌（f-P. acnes）以不同的感染复数比例孵育。用实时定量 RT-PCR 测量 AhR 下游细胞色素 P450（CYP）基因的 mRNA 水平，用 Western blot 和免疫荧光法测量 AhR 的核易位，用基因集富集分析（GSEA）测量脂肪生成和角化，用油红 O 染色和尼罗红染色进行脂质相关分析，用 Western blot 检测皮脂分化相关基因的表达。
f-P. acnes 上调了 CYP 的 mRNA 水平，并诱导 AhR 蛋白从细胞质向细胞核易位。GSEA 显示脂肪生成下调，角化上调。f-P. acnes 抑制了亚油酸诱导的中性脂质合成和皮脂腺标记物角蛋白 7 和粘蛋白 1/EMA 的表达，但增加了角蛋白细胞标记物角蛋白 10 和内披蛋白的表达，这些表达被 AhR 基因沉默所抑制。还观察到脂生成相关基因如固醇反应元件结合蛋白的抑制。
f-P. acnes 通过体外激活 AhR 通路抑制脂肪生成，并诱导皮脂腺细胞向角蛋白细胞样细胞的终末分化，提示毛囊中的 P. acnes 不仅具有致痤疮作用，而且通过皮脂生成的反馈调节促进痤疮消退。
