中国免疫学杂志2025，Vol.41Issue(4)：861-866,6.DOI:10.3969/j.issn.1000-484X.2025.04.015
自噬通过下调ATF6通路抑制促炎型巨噬细胞活化
Autophagy inhibits activation of pro-inflammatory macrophages by suppressing ATF6 pathway
摘要
Abstract
Objective:To explore the potential mechanisms of autophagy suppressing the activation of pro-inflammatory macro-phages.Methods:Macrophage-specific knockout mice(Atg5△mye)was generated by the hybridization of Lyz2-Cre mice and Atg 5flox/+mice.Bone marrow cells were differentiated into bone marrow-derived macrophages(BMDMs)induced by monocyte colony-stimulating factor.The expressions of endoplasmic reticulum stress(ER stress)-related proteins,such as glucose regulatory protein 78(GRP78),autophagy-related marker LC3-Ⅱ and p62,and pro-inflammatory iNOS,were detected by Western blot.GO analysis was performed on BMDMs from Atg5flox/flox and Atg5△mye mice stimulated by LPS.Tauroursodeoxycholate(TUDCA)or ATF6 inhibitor Ceapin-A7 was used to suppress the ER stress in BMDMs.Results:LPS promoted the expression of ER stress-related proteins and the activation of pro-in-flammatory macrophages,while inhibiting autophagy in BMDMs.By utilizing proteomic detection and GO enrichment analysis,it was found that the autophagy deficiency in BMDMs caused changes in the ATF6 pathway,a key downstream pathway of ER stress.Inhibi-tion of ER stress by TUDCA significantly down-regulated the expression of iNOS and the secretion of inflammatory cytokines IL-18 and IL-1β in autophagy-deficient BMDMs.ATF6-specific inhibitor(Ceapin-A7)was used to exculpate LPS-stimulated BMDMs,and it was found that Ceapin-A7 significantly down-regulated the elevated expression of iNOS and inflammatory factors caused by Atg5 deletion in BMDMs.Conclusion:Autophagy inhibits the activation of pro-inflammatory macrophages by suppressing ATF6 pathway.关键词
巨噬细胞/自噬/内质网应激/炎症反应Key words
Macrophage/Autophagy/Endoplasmic reticulum stress/Inflammatory response分类
医药卫生引用本文复制引用
李慧媛,黄小荣,黄丽凤,杨陈,安宁..自噬通过下调ATF6通路抑制促炎型巨噬细胞活化[J].中国免疫学杂志,2025,41(4):861-866,6.基金项目
广东省基础与应用基础研究基金(2023A1515030024,2021A1515011581) （2023A1515030024,2021A1515011581）
省市共建细胞自噬与慢性重大非传染性疾病研究广东省重点实验室项目(2022B1212030003) （2022B1212030003）
国家临床重点专科建设(肾病科)单位项目. （肾病科）
