Aryl Hydrocarbon Receptor Modulates the Expression of TNF-α and IL-8 in Human Sebocytes via the MyD88-p65NF-κB/p38MAPK Signaling Pathways
Aryl Hydrocarbon Receptor Modulates the Expression of TNF-α and IL-8 in Human Sebocytes via the MyD88-p65NF-κB/p38MAPK Signaling Pathways
复制标题
芳基烃受体通过 MyD88-p65NF-κB/p38MAPK 信号通路调节人皮脂细胞中 TNF-α 和 IL-8 的表达
DOI：
10.1159/000491029
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发表时间：
2019-01-01
影响因子：
5.3
通讯作者：
Ju, Qiang
中科院分区：
文献类型：
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作者：
Hou, Xiao-Xiao;Chen, Guangjie;Ju, Qiang
Toll样受体（TLR）-2的激活和随后的炎症反应有助于寻常痤疮的病变发展。芳烃受体（AhR），细胞溶质受体蛋白，响应于环境和生理应激，和TLR之间的串扰最近已被报道。在这项研究中，我们探讨了AhR在肽聚糖（PGN），一个经典的TLR 2激动剂诱导的人SZ 95皮脂腺细胞的影响的可能作用。AhR抑制剂CH 223191预处理和AhR敲低后，PGN诱导的人SZ 95皮脂腺细胞分泌炎性因子TNF-α和IL-8受到抑制。此外，AhR激动剂2，3，7，8-四氯二苯并对二恶英（TCDD）可促进PGN预处理的皮脂腺细胞分泌TNF-α和IL-8。此外，TCDD增强了PGN诱导的骨髓分化因子88（MyD 88）、磷酸化p38 MAPK（p-p38 MAPK）和p-p65 NF-κB的表达，并被CH 223191抑制。抑制AhR表达的shRNA阻断了PGN刺激SZ 95皮脂腺细胞p38 MAPK和p65 NF-κB磷酸化的能力。结论：AhR通过MyD 88-p65 NF-κB/p38 MAPK信号通路调节PGN诱导的人SZ 95皮脂腺细胞TNF-α和IL-8的表达，提示AhR可能是TLR 2介导痤疮的一种新机制。
Activation of Toll-like receptor (TLR)-2 and subsequent inflammatory response contribute to lesion development in acne vulgaris. A cross-talk between aryl hydrocarbon receptor (AhR), a cytosolic receptor protein that responds to environmental and physiological stress, and TLRs has recently been reported. In this study, we explored the possible role of AhR in the effects induced on cultured human SZ95 sebocytes by peptidoglycan (PGN), a classic TLR2 agonist. PGN-induced secretion of inflammatory factors TNF-α and IL-8 in human SZ95 sebocytes was suppressed after knockdown of AhR and pretreatment with the AhR antagonist CH223191. In addition, the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhanced TNF-α and IL-8 secretion in PGN-pretreated sebocytes. Furthermore, PGN-induced expression of myeloid differentiation factor 88 (MyD88), phospho-p38MAPK (p-p38MAPK), and p-p65NF-κB was strengthened by TCDD and repressed by CH223191. AhR inhibition by transfecting shRNA blocked the ability of PGN to stimulate phosphorylation of p38MAPK and p65NF-κB in SZ95 sebocytes. Overall, these data demonstrate that AhR is able to modulate PGN-induced expression of TNF-α and IL-8 in human SZ95 sebocytes involving the MyD88-p65NF-κB/p38MAPK signaling pathway, which probably indicates a new mechanism in TLR2-mediated acne.