文献类型：期刊文献

英文题名：Arsenite inhibits M2a polarization of macrophages through downregulation of peroxisome proliferator-activated receptor gamma

作者：Li, Dan[1,2];Ma, Huijuan[1,2];Shu, Qi[1,2];Wang, Tingqian[1,2];Li, Linyi[1,2];Huang, Ping[1,2];Lou, Kaiyan[1,2];Xu, Huan[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontiers Sci Ctr Optogenet Tech Cell Met, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2022

卷号：450

外文期刊名：TOXICOLOGY AND APPLIED PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000826298500001)】；

基金：This work was funded by National Natural Science Foundation of China [grant No. 42177417 to H. X., grant No. 21906057 to H. X., grant No. 21577037 to K. L.] . This work was also funded by Shanghai Sailing Program [grant No. 19YF1412500 to H. X.] and Shanghai Natural Sci-ence Fund [grant No. 20ZR1414700 to K. L.] from the Shanghai Science and Technology Committee. This work was also supported by Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission) . The manuscript is dedi-cated to Dr. Scott Burchiel.

语种：英文

外文关键词：Arsenite; PPAR-?; M2a polarization; Macrophages; Immunosuppression; Rosiglitazone

摘要：Arsenite (As+3) is a group one human carcinogen, which has been associated with many diseases. Previous studies indicated that As+3 could inhibit wound healing and repair. M2a cells are known as tissue remodeling macrophages, which play an important role in wound repair process. Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a key regulator of lipid and glucose metabolism, was found to mediate the IL-4-dependent M2a polarization of macrophages. In the present study, As+3 induced dose-dependent inhibition of M2a polarization starting from 0.1 mu M in THP-1-derived macrophages stimulated with 20 ng/mL IL-4. Increased lipid accumulation and decreased PPAR-gamma expression were also observed in As+3-treated M2a macrophages. Rosiglitazone (RSG), a potent PPAR-gamma agonist, alleviated the suppressions of PPAR-gamma and M2a polarization induced by 2 mu M As+3. Collectively, these results not only demonstrated that As+3 was able to inhibit polarization of M2a cells through PPAR-gamma suppression, but also indicated that PPAR-gamma could be utilized as a target for the prevention and treatment of As+3-induced immunotoxicity.