Eicosapentaenoic Acid (EPA) Induced Macrophages Activation Through GPR120-Mediated Raf-ERK1/2-IKKβ-NF-κB P65 Signaling Pathways
Overview
Affiliations
To investigate the immunomodulatory effect and molecular mechanisms of Eicosapentaenoic acid (EPA, a typical kind of n-3PUFAs) on RAW264.7 cells. A variety of research methods, including the RAW264.7 cells culture, cell proliferation assays, morphologic observations, measurements of NO production, cytokine assays, nuclear protein extractions, western blot analyses and NF-κB p65 immunofluorescence assays were used in this study. The results showed that EPA could increase the proliferation index and enhance the release of nitric oxide (NO) and cytokines in RAW264.7 cells. Western blotting results revealed that the protein level of GPR120 increased significantly in RAW264.7 cells after EPA treatment. Meanwhile, EPA elevated the phosphorylation status of Raf, which may act as an upstream regulator of EPA-induced phosphorylated ERK1/2. In addition, the phosphorylated ERK1/2 may then promote IKKβ in endochylema and translocate the NF-κB p65 subunit into the nucleus, thus regulating the production of inducible nitric oxide synthase (iNOS) and cytokines. EPA (0.6-3.0 μmol) activates RAW264.7 cells through GPR120-mediated Raf-ERK1/2-IKKβ-NF-κB p65 signaling pathways.
Eicosapentaenoic acid induces macrophage Mox polarization to prevent diabetic cardiomyopathy.
Li J, Nan W, Huang X, Meng H, Wang S, Zheng Y EMBO Rep. 2024; 25(12):5507-5536.
PMID: 39482491 PMC: 11624267. DOI: 10.1038/s44319-024-00271-x.
Melatonin Alters the miRNA Transcriptome of Inflammasome Activation in Murine Microglial Cells.
Tarakcioglu E, Tastan B, Arioz B, Tufekci K, Genc S Neurochem Res. 2022; 47(10):3202-3211.
PMID: 35842554 DOI: 10.1007/s11064-022-03674-1.
Qiu T, Yang X, Wang J, Pan C, Chu X, Xiong J Nutr Diabetes. 2022; 12(1):23.
PMID: 35443706 PMC: 9021212. DOI: 10.1038/s41387-022-00202-6.
Zhou C, He X, Tong C, Li H, Xie C, Wu Y Int J Biol Sci. 2022; 18(4):1363-1380.
PMID: 35280694 PMC: 8898379. DOI: 10.7150/ijbs.65227.
GPR120/FFAR4 Pharmacology: Focus on Agonists in Type 2 Diabetes Mellitus Drug Discovery.
Carullo G, Mazzotta S, Vega-Holm M, Iglesias-Guerra F, Vega-Perez J, Aiello F J Med Chem. 2021; 64(8):4312-4332.
PMID: 33843223 PMC: 8154576. DOI: 10.1021/acs.jmedchem.0c01002.