IRE1α regulates macrophage polarization in type 2 diabetic periodontitis through promoting endoplasmic reticulum stress

作者全名：Zhang, Yang; Zhang, Yanan; Lu, Miao; Yuan, Xulei; Li, Guangyue; Xu, Ling; Zhang, Tingwei; Song, Jinlin

作者地址：[Zhang, Yang; Zhang, Yanan; Lu, Miao; Yuan, Xulei; Li, Guangyue; Xu, Ling] Chongqing Med Univ, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Zhang, Tingwei; Song, Jinlin] Chongqing Med Univ, Stomatol Hosp, 426 Songshibei Rd, Chongqing 401147, Peoples R China

通信作者：Zhang, TW; Song, JL (通讯作者)，Chongqing Med Univ, Stomatol Hosp, 426 Songshibei Rd, Chongqing 401147, Peoples R China.

来源：INTERNATIONAL IMMUNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001230524700001

JCR分区：Q1

影响因子：4.8

年份：2024

卷号：133

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Diabetes mellitus; Periodontitis; IRE1 alpha; Macrophages; Endoplasmic reticulum stress

摘要：Objectives: The aim of this study was to investigate the effect of 4 mu 8c, an inhibitor targeting the endoplasmic reticulum stress-associated factor IRE1 alpha, on macrophage polarization in an experimental model of diabetic periodontitis through ex vivo experiments. Materials and methods: Local alveolar bone parameters were evaluated using Micro-CT following intraperitoneal administration of 4 mu 8c in mice with experimental diabetic periodontitis. Surface markers indicating macrophage polarization were identified using immunofluorescence. In vitro experiments were performed employing bone marrow-derived macrophages and gingival fibroblasts. Macrophage polarization was determined using flow cytometry. Principal impacted signaling pathways were identified through Western blot analysis. Results: Results from both in vitro and in vivo experiments demonstrated that 4 mu 8c mitigated alveolar bone resorption and inflammation in mice with diabetic periodontitis. Furthermore, it modulated macrophage polarization towards the M2 phenotype and augmented M2 macrophage polarization through the MAPK signaling pathway. Conclusions: These findings suggest that inhibiting IRE1 alpha can modulate macrophage polarization and alleviate ligature-induced diabetic periodontitis via the MAPK signaling pathway. This unveils a novel mechanism, offering a scientific foundation for the treatment of experimental diabetic periodontitis.

基金机构：National Key Research and Development Program of China [2022YFC2504200]; National Natural Science Foundation of China [82170968, 31971282, U22A20314]; Chongqing Graduate Tutor Team Construction Project

基金资助正文：This work was supported by grants from the National Key Research and Development Program of China (Grant no. 2022YFC2504200) , the National Natural Science Foundation of China (Grant nos. 82170968, 31971282, U22A20314) and the Chongqing Graduate Tutor Team Construction Project (Grant no. dstd201903) .