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

Abstract

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.

Large Yellow Tea Polysaccharide Alleviates HFD-Induced Intestinal Homeostasis Dysbiosis via Modulating Gut Barrier Integrity, Immune Responses, and the Gut Microbiome

“…Notably, we found that consumption of LYP promoted the expression of GLP-1 in the small intestine. Emerging evidence has suggested that GLP-1 could enhance intestinal barrier function and regulate macrophage polarization. , Consistent with the reported study, our results verified that LYP intervention remarkably up-regulated the expression of GLP-1, promoted polarization of M2, and protected the intestinal barrier function. However, additional studies are needed to clarify the detailed mechanism underlying the effects of LYP on GLP-1 secretion and expression.…”

Urate Biology and Biochemistry: A Year in Review 2022

“…Novel findings regarding the basic biochemistry/biology of UA in the context of gout published over the past year were not abundant but do include a report demonstrating a role for glucagon-like peptide-1 (GLP-1) and its receptor GLP-1R in the inflammatory response to monosodium urate crystals [16]. This study demonstrated GLP-1R expression in murine macrophages with greater expression in M2 and Ly6C+ macrophages than their corresponding counterparts.…”

GLP-1 receptor agonist as a modulator of innate immunity

“…The expression of GLP-1R remains controversial due to the lack of specific antibody against GLP-1R, with most of the literatures using qPCR to detect mRNA levels ( 24 , 25 ). There were also a few studies detected the expression of GLP-1R at the protein level using a lineage-tracking animal model ( 26 , 27 ). Although Glp1r mRNA transcripts have been detected in murine lymphoid tissue, little is known about the role of GLP-1 in the immune system ( 28 ).…”