Glucagon-like peptide-1 modulates RAW264.7 macrophage polarization by interfering with the JNK/STAT3 signaling pathway.

Abstract

Insulin resistance and metabolic disorders are closely associated with low-grade chronic inflammation. Aberrant macrophage activation to M1 or M2 is characterized by a deleterious state of chronic inflammation and loss of positive trophic signals. Glucagon-like peptide-1 (GLP-1) is used to treat diabetes due to its beneficial role against insulin resistance. The present study examined the effect of GLP-1 on macrophage activation, which contributed to M2 polarization and secretion of anti-inflammatory factors. In addition, the present study demonstrated that GLP-1 was able to reduce M1 polarization and inflammatory response by using the murine monocyte/macrophage cell line RAW264.7 and detecting M1/M2-specific genes. RAW264.7 cells were incubated with GLP-1 in the presence or absence of lipopolysaccharide or interleukin-4, the c-Jun N-terminal kinase (JNK) and signal transduction and transcriptional activation factor 3 (STAT3) activity was assessed by quantification of phosphorylation expression and macrophage polarization was determined by detecting M1/M2-specific genes expression. The results demonstrated that GLP-1/GLP-1 receptor attenuated the phosphorylation of JNK and its signal transduction through the cyclic adenosine monophosphate/protein kinase A signaling pathway, while the phosphorylation of STAT3 increased through following treatment with GLP-1. The present study observed that GLP-1 exerts its beneficial effects on macrophage polarization by modulating the JNK/STAT3 signaling pathway. The present results also suggested that the effects of GLP-1 on endocrine and metabolic diseases are possibly mediated by modulation of signaling pathways, and provide a basis for pharmacologic targeting of macrophage activation and an insight into the molecular mechanisms involved in the progression of metabolic diseases.