Formalin-killed Propionibacterium acnes activates the aryl hydrocarbon receptor and modifies differentiation of SZ95 sebocytes in vitro
Formalin-killed Propionibacterium acnes activates the aryl hydrocarbon receptor and modifies differentiation of SZ95 sebocytes in vitro
复制标题
福尔马林灭活的痤疮丙酸杆菌在体外激活芳基烃受体并改变 SZ95 皮脂腺细胞的分化
DOI：
10.1684/ejd.2021.3964
复制
发表时间：
2021-01-01
影响因子：
2.5
通讯作者：
Ju, Qiang
中科院分区：
文献类型：
--
作者：
Cao, Ke;Chen, Guangjie;Ju, Qiang
寻常痤疮是一种与痤疮丙酸杆菌（P. acnes）相关的常见毛囊皮脂腺疾病。粉刺的消退可能与含有去分化细胞的皮脂腺（SGs）萎缩有关，但痤疮痤疮的作用尚不清楚。目的探讨痤疮芽孢杆菌对培养的人SZ95永生化脂细胞芳烃受体（AhR）激活、脂肪生成和分化的影响。材料与方法将培养的皮脂细胞与福尔马林杀死的痤疮P. （f-）进行孵育。痤疮)在不同比例的多重感染。定量RT-PCR检测AhR下游细胞色素P450 （CYP）基因mRNA水平，western blot和免疫荧光检测AhR核易位，基因集富集分析（GSEA）检测脂肪生成和角化，油红O染色和尼罗红染色检测脂质相关，western blot检测皮脂腺分化相关基因表达。.结果。痤疮上调CYPs mRNA水平，诱导AhR蛋白从细胞质转位到细胞核。GSEA显示脂肪生成下调和角化上调。.。痤疮抑制亚油酸诱导的中性脂合成和脂质细胞标志物、角蛋白7和mucin1/EMA的表达，但增加角化细胞标志物、角蛋白10和天花素的表达，这些被AhR基因沉默所消除。脂肪生成相关基因的抑制，如固醇反应元件结合蛋白，也被观察到。.结论。痤疮在体外通过激活AhR通路抑制脂肪生成，诱导皮脂细胞最终分化为角化细胞样细胞，提示毛囊性痤疮痤疮不仅是痤疮源性的，而且通过反馈调节皮脂生成促进痤疮缓解。
Background 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. Objectives 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. Results 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. Conclusion 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.