RRC ID 52110
Author Inoue T, Tanaka M, Masuda S, Ohue-Kitano R, Yamakage H, Muranaka K, Wada H, Kusakabe T, Shimatsu A, Hasegawa K, Satoh-Asahara N.
Title Omega-3 polyunsaturated fatty acids suppress the inflammatory responses of lipopolysaccharide-stimulated mouse microglia by activating SIRT1 pathways.
Journal Biochim Biophys Acta Mol Cell Biol Lipids
Abstract Obesity and diabetes are known risk factors for dementia, and it is speculated that chronic neuroinflammation contributes to this increased risk. Microglia are brain-resident immune cells modulating the neuroinflammatory state. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the major ω-3 polyunsaturated fatty acids (PUFAs) of fish oil, exhibit various effects, which include shifting microglia to the anti-inflammatory phenotype. To identify the molecular mechanisms involved, we examined the impact of EPA, DHA, and EPA+DHA on the lipopolysaccharide (LPS)-induced cytokine profiles and the associated signaling pathways in the mouse microglial line MG6. Both EPA and DHA suppressed the production of the pro-inflammatory cytokines TNF-α and IL-6 by LPS-stimulated MG6 cells, and this was also observed in LPS-stimulated BV-2 cells, the other microglial line. Moreover, the EPA+DHA mixture activated SIRT1 signaling by enhancing mRNA level of nicotinamide phosphoribosyltransferase (NAMPT), cellular NAD+ level, SIRT1 protein deacetylase activity, and SIRT1 mRNA levels in LPS-stimulated MG6. EPA+DHA also inhibited phosphorylation of the stress-associated transcription factor NF-κB subunit p65 at Ser536, which is known to enhance NF-κB nuclear translocation and transcriptional activity, including cytokine gene activation. Further, EPA+DHA increased the LC3-II/LC3-I ratio, an indicator of autophagy. Suppression of TNF-α and IL-6 production, inhibition of p65 phosphorylation, and autophagy induction were abrogated by a SIRT1 inhibitor. On the other hand, NAMPT inhibition reversed TNF-α suppression but not IL-6 suppression. Accordingly, these ω-3 PUFAs may suppress neuroinflammation through SIRT1-mediated inhibition of the microglial NF-κB stress response and ensue pro-inflammatory cytokine release, which is implicated in NAMPT-related and -unrelated pathways.
Volume 1862(5)
Pages 552-560
Published 2017-5-1
DOI 10.1016/j.bbalip.2017.02.010
PII S1388-1981(17)30034-3
PMID 28254441
MeSH Animals Cytokines / biosynthesis Docosahexaenoic Acids / metabolism Eicosapentaenoic Acid / metabolism Fatty Acids, Omega-3 / metabolism* Fish Oils / metabolism Inflammation / chemically induced Inflammation / genetics Inflammation / metabolism* Inflammation / pathology Lipopolysaccharides / toxicity Mice Microglia / drug effects Microglia / metabolism* Microglia / pathology Nicotinamide Phosphoribosyltransferase / biosynthesis Risk Factors Signal Transduction Sirtuin 1 / biosynthesis* Sirtuin 1 / genetics Tumor Necrosis Factor-alpha / biosynthesis
IF 4.402
Times Cited 42
Human and Animal Cells MG6(RCB2403)