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Omega-3 Free Fatty Acids Suppress Macrophage Inflammasome Activation by Inhibiting NF-κB Activation and Enhancing Autophagy
Open accessAbstract
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.
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“n-3 PUFAs, in addition to modulating eicosanoid synthesis, can also inhibit the activation of NFκB in skeletal muscle cells and other cell types in vitro (see Section 2.3) [69,70,71,72].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [71]
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Metadata
- Authors
- Williams-Bey, Y., Boularan, C., Vural, A., Huang, N.-N., Hwang, I.-Y., Shan-Shi, C., & Kehrl, J. H.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Kehrl, John H.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-06-09
- Volume
- 9
- Issue
- 6
- Pages
- e97957
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4049592
- OpenAlex
- W2062456565
- Cited by
- 215
- References
- 18
- Citations by year
- 2026: 15 · 2025: 12 · 2024: 10 · 2023: 11 · 2022: 19 · 2021: 28 · 2020: 23 · 2019: 13 · 2018: 19 · 2017: 19 · 2016: 21 · 2015: 23 · 2014: 2
- FWCI
- 8.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- docosahexaenoic acid, omega-3 fatty acids, macrophages, inflammasome activation, IL-1β production, NLRP3 inflammasome, AIM2 inflammasome, free fatty acid receptor 4, GPR120, NF-κB nuclear translocation, autophagy, ATG7
- MeSH terms
- beta-Arrestins, Animals, Autophagy, Bone Marrow Cells, Calcium, Cell Nucleus, Docosahexaenoic Acids, Gene Expression Regulation, HeLa Cells, Humans, Lipopolysaccharides, Macrophage Activation, Macrophages, Mice, Inbred C57BL, NF-kappa B, Arrestins, Active Transport, Cell Nucleus, Intracellular Space, Receptors, G-Protein-Coupled, Mice, Interleukin-1beta, Inflammasomes
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