| First Author | Williams-Bey Y | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 6 | Pages | e97957 |
| PubMed ID | 24911523 | Mgi Jnum | J:218571 |
| Mgi Id | MGI:5617925 | Doi | 10.1371/journal.pone.0097957 |
| Citation | Williams-Bey Y, et al. (2014) Omega-3 free fatty acids suppress macrophage inflammasome activation by inhibiting NF-kappaB activation and enhancing autophagy. PLoS One 9(6):e97957 |
| abstractText | The omega-3 (omega3) fatty acid docosahexaenoic acid (DHA) can suppress inflammation, specifically IL-1beta production through poorly understood molecular mechanisms. Here, we show that DHA reduces macrophage IL-1beta production by limiting inflammasome activation. Exposure to DHA reduced IL-1beta 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 beta-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-kappaB. DHA also reduced IL-1beta 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. |
