Autophagy inhibits activation of pro-inflammatory macrophages by suppressing ATF6 pathway
10.3969/j.issn.1000-484X.2025.04.015
- VernacularTitle:自噬通过下调ATF6通路抑制促炎型巨噬细胞活化
- Author:
Huiyuan LI
1
;
Xiaorong HUANG
1
;
Lifeng HUANG
1
;
Chen YANG
1
;
Ning AN
1
Author Information
1. 广东医科大学附属医院肾病研究所,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,湛江 524001
- Publication Type:Journal Article
- Keywords:
Macrophage;
Autophagy;
Endoplasmic reticulum stress;
Inflammatory response
- From:
Chinese Journal of Immunology
2025;41(4):861-866
- CountryChina
- Language:Chinese
-
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.
