論文 - 詳細
| RRC ID | 52110 |
|---|---|
| 著者 | Inoue T, Tanaka M, Masuda S, Ohue-Kitano R, Yamakage H, Muranaka K, Wada H, Kusakabe T, Shimatsu A, Hasegawa K, Satoh-Asahara N. |
| タイトル | Omega-3 polyunsaturated fatty acids suppress the inflammatory responses of lipopolysaccharide-stimulated mouse microglia by activating SIRT1 pathways. |
| ジャーナル | 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. |
| 巻・号 | 1862(5) |
| ページ | 552-560 |
| 公開日 | 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 |
| 引用数 | 42 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 254 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MG6(RCB2403) |