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标题：IL-10 attenuates OxPCs-mediated lipid metabolic responses in ischemia reperfusion injury
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作者：Ashim K. Bagchi ; Arun Surendran ; Akshi Malik 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
DOI：10.1038/s41598-020-68995-z
出版社：Springer Nature
摘要：Oxidized phospholipids (OxPLs) promote inflammation as well as low density lipoprotein (LDL) uptake in a variety of physiological and pathological states. Given the anti-inflammatory role of the cytokine IL-10, we investigated its modulatory effect on the production of oxidized phosphatidylcholines (OxPCs) as well as lipid metabolic responses in global myocardial ischemia/reperfusion (I/R) injury. Increased OxPCs levels, by 1-Palmitoyl-2-(5-oxovaleryl)-sn-glycero-3-phosphocholine (POVPC), promoted oxidative stress (OS) and cell death. OxPCs-mediated-OS, resulted in oxidized low-density lipoprotein receptor 1 (LOX-1) activation and upregulated the expression of toll-like receptor 2 (TLR2). IL-10-induced increase in proprotein convertase subtilisin/kexin type 9 (PCSK9) negatively regulated LOX-1 as well as TLR2 inflammatory responses. Under stress conditions, phosphorylation of sterol regulatory element binding protein 1c (SREBP 1c) was prevented by IL-10. The latter also prevented the generation of OxPCs and reduced their ratio (OxPCs/PCs) during injury. LOX-1 activation also promoted SREBP1c-mediated TGF-βRII expression which was inhibited by IL-10. Both fragmented and non-fragmented OxPCs were elevated during I/R and this effect was attenuated by IL-10. The largest impact (two–threefold change at log2) was on PAzPC, (1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine)—a fragmented OxPC. Thus it appears that among different OxPCs, IL-10 significantly reduces a single molecule (PAzPC)-mediated lipid metabolic responses in cardiomyocytes thereby mitigating inflammation and cell death.