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

Wan,Shan; Sun,Hui

doi:10.3892/etm.2019.7347

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

Authors:
- Shan Wan
- Hui Sun
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Affiliations: Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: March 6, 2019 https://doi.org/10.3892/etm.2019.7347
Pages: 3573-3579
Copyright: © Wan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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