Glucagon-Like Peptide-1 Receptor Regulates Macrophage Migration in Monosodium Urate-Induced Peritoneal Inflammation

Frontiers in Immunology

Immunology

Sanjay Rajagopalan¹  Lihua Duan¹  Biao Wang²  Yingying Wei³  Xiaoquan Rao⁴  Zachary Braunstein⁵  Xinxin Liu⁶  Jixin Zhong⁶  Lingli Dong⁶  Aihua Mei⁷  Jun Chen⁸ 

[1] Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United States;Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United States;Department of Biochemistry and Molecular Biology, School of Life Sciences, China Medical University, Shenyang, China;Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United States;Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China;Department of Cardiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China;Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, United States;Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China;Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China;Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China;Cardiovascular Research Institute, Case Western Reserve University, Cleveland, OH, United States;

关键词: gout;    GLP-1, glucagon-like peptide-1;    macrophage;    monosodium urate;    inflammation;   

DOI  :  10.3389/fimmu.2022.772446

 received in 2021-09-08, accepted in 2022-01-07,  发布年份 2022

来源: Frontiers

【 摘 要 】

Glucagon-like peptide-1 (GLP-1) is an insulinotropic peptide that signals through the GLP-1 receptor (GLP-1R). GLP-1R, therefore, plays a critical role in diabetes and cardiovascular disease. Whether GLP-1R is involved in inflammatory disease such as gout remains unclear. Macrophages are critical effector cells in the pathogenesis of gout, a common form of inflammatory arthritis caused by the deposition of uric acid in joints. The expression of GLP-1R at the protein level is controversial due to the lack of specificity of existing antibodies against GLP-1R. Using a transgenic mouse model expressing enhanced green fluorescent protein (EGFP) under the control of GLP-1R promoter, here we confirmed the expression of GLP-1R by macrophages. M2 type macrophages and Ly6C+ macrophages expressed higher levels of GLP-1R, compared to their counterparts. GLP-1R deficient macrophages displayed a reduced the migratory ability and an enhanced expression of interleukin (IL)-6, while the expression of IL-1β was not affected. In monosodium urate (MSU) crystal-induced peritonitis, an experimental model of gout, the recruitment of macrophages, especially M2 macrophages, was significantly suppressed in GLP-1R knockout mice compared to wild-type mice. In conclusion, our data suggests that GLP-1R plays a critical role in macrophage migration in MSU-induced inflammation.

【 授权许可】

Unknown   
Copyright © 2022 Chen, Mei, Liu, Braunstein, Wei, Wang, Duan, Rao, Rajagopalan, Dong and Zhong