Immunomodulatory Activity of Docosahexenoic Acid on RAW264.7 Cells Activation through GPR120-Mediated Signaling Pathway

J Agric Food Chem. 2018 Jan 31;66(4):926-934. doi: 10.1021/acs.jafc.7b05894. Epub 2018 Jan 18.

Abstract

In this study, we elucidated the immunomodulatory activity of docosahexaenoic acid (DHA) on protein expression in RAW264.7 cells and its molecular mechanism. The results showed that the proliferation index of RAW264.7 cells at 48 h was about 173.03 ± 7.82% after the treatment of 2.4 μM DHA. DHA could activate RAW264.7 cells by the G-protein coupled cell membrane receptor GPR120-C-Raf- mitogen-activated protein kinases (MAPKs)-nuclear factor κB (NF-κB) p65 pathway. In addition, 2.4 μM of DHA could significantly increase (P < 0.01) the mRNA and protein expression of inducible nitric oxide synthase (iNOS), which is consistent with the result of the NO release. ELISA results revealed that DHA could enhance the protein expression of cytokines IL-1β, IL-6, IL-10, IL-12, TNF-α, IFN-γ, and TGF-β. These results indicated that the immunomodulatory mechanism of RAW264.7 cells by DHA was associated with the release of NO and cytokines by stimulating the GPR120, C-Raf, and MAPKs to the NF-κB p65 pathway.

Keywords: GPR120; NF-κB p65; RAW264.7 cells; docosahexaenoic acid; immunomodulatory.

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Docosahexaenoic Acids / pharmacology*
  • Immunologic Factors / pharmacology*
  • Macrophage Activation / drug effects*
  • Mice
  • Mitogen-Activated Protein Kinases / physiology
  • Nitric Oxide / metabolism
  • Proto-Oncogene Proteins c-raf / physiology
  • RAW 264.7 Cells
  • Receptors, G-Protein-Coupled / physiology*
  • Signal Transduction
  • Transcription Factor RelA / physiology

Substances

  • Cytokines
  • FFAR4 protein, mouse
  • Immunologic Factors
  • Receptors, G-Protein-Coupled
  • Rela protein, mouse
  • Transcription Factor RelA
  • Docosahexaenoic Acids
  • Nitric Oxide
  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinases