Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-κB activation and enhancing autophagy

PLoS One. 2014 Jun 9;9(6):e97957. doi: 10.1371/journal.pone.0097957. eCollection 2014.


The omega-3 (ω3) fatty acid docosahexaenoic acid (DHA) can suppress inflammation, specifically IL-1β production through poorly understood molecular mechanisms. Here, we show that DHA reduces macrophage IL-1β production by limiting inflammasome activation. Exposure to DHA reduced IL-1β production by ligands that stimulate the NLRP3, AIM2, and NAIP5/NLRC4 inflammasomes. The inhibition required Free Fatty Acid Receptor (FFAR) 4 (also known as GPR120), a G-protein coupled receptor (GPR) known to bind DHA. The exposure of cells to DHA recruited the adapter protein β-arrestin1/2 to FFAR4, but not to a related lipid receptor. DHA treatment reduced the initial inflammasome priming step by suppressing the nuclear translocation of NF-κB. DHA also reduced IL-1β levels by enhancing autophagy in the cells. As a consequence macrophages derived from mice lacking the essential autophagy protein ATG7 were partially resistant to suppressive effects of DHA. Thus, DHA suppresses inflammasome activation by two distinct mechanisms, inhibiting the initial priming step and by augmenting autophagy, which limits inflammasome activity.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Arrestins / metabolism
  • Autophagy / drug effects*
  • Bone Marrow Cells / cytology
  • Calcium / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Docosahexaenoic Acids / pharmacology*
  • Gene Expression Regulation / drug effects
  • HeLa Cells
  • Humans
  • Inflammasomes / metabolism*
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / metabolism
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects*
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • beta-Arrestins


  • Arrestins
  • FFAR4 protein, mouse
  • Inflammasomes
  • Interleukin-1beta
  • Lipopolysaccharides
  • NF-kappa B
  • Receptors, G-Protein-Coupled
  • beta-Arrestins
  • Docosahexaenoic Acids
  • Calcium