title: Glucagon-like peptide-1 (GLP-1) induces M2 polarization of human macrophages via STAT3 activation.
abstract: It is known that glucagon-like peptide-1 (GLP-1) is a hormone secreted postprandially from the L-cells of the small intestine and regulates glucose homeostasis. GLP-1 is now used for the treatment of diabetes because of its beneficial role against insulin resistance. The GLP-1 receptor (GLP-1R) is expressed on many cell types, including macrophages, and GLP-1 suppresses the development of atherosclerosis by inhibiting macrophage function. However, there have so far been few studies that have investigated the significance of GLP-1/GLP-1R signaling in macrophage activation. In the present study, we examined the effect of GLP-1 and exenatide, a GLP-1R agonist, on human monocyte-derived macrophage (HMDM) activation. We found that GLP-1 induced signal transducer and activator of transcription 3 (STAT3) activation. Silencing of GLP-1R suppressed the GLP-1-induced STAT3 activation. In addition, alternatively activated (M2) macrophage-related molecules, such as IL-10, CD163, and CD204 in HMDM, were significantly upregulated by GLP-1. Furthermore, the co-culture of 3T3-L1 adipocytes with GLP-1-treated RAW 264.7 macrophages increased the secretion of adiponectin compared to co-culture of the 3T3-L1 adipocytes with untreated RAW 264.7 macrophages. Our results demonstrate that GLP-1 induces macrophage polarization toward the M2 phenotype, which may contribute to the protective effects of GLP-1 against diabetes and cardiovascular diseases.
authors: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Kumamoto, Japan.
authors: Daisuke
authors: D
authors: Shiraishi
authors: Yukio
authors: Y
authors: Fujiwara
authors: Yoshihiro
authors: Y
authors: Komohara
authors: Hiroshi
authors: H
authors: Mizuta
authors: Motohiro
authors: M
authors: Takeya
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D016764:Cell Polarity; D000077270:Exenatide; D020868:Gene Silencing; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D016753:Interleukin-10 / Q000819:agonists / Q000096:biosynthesis; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000819:agonists / Q000096:biosynthesis; D018027:Receptors, Glucagon / Q000819:agonists / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000819:agonists*; D051117:Scavenger Receptors, Class A / Q000819:agonists / Q000096:biosynthesis; D014688:Venoms / Q000494:pharmacology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; C495139:MSR1 protein, human; D010455:Peptides; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051117:Scavenger Receptors, Class A; D014688:Venoms; D016753:Interleukin-10; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide