IL-10 attenuates OxPCs-mediated lipid metabolic responses in ischemia reperfusion injury.

Scientific Reports
Ashim K BagchiPawan K Singal

Abstract

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 effe...Continue Reading

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Citations

Apr 4, 2021·International Journal of Molecular Sciences·Zoran TodorovićJelena Đorđević
Apr 16, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Ashim K BagchiPawan K Singal
Aug 1, 2021·American Journal of Reproductive Immunology : AJRI·Alexandra D GoudreauKristi B Adamo

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Methods Mentioned

BETA
acetylation
immunoprecipitation
nuclear translocation
fluorescence microscopy

Software Mentioned

AxioVision
ImageJ
Quantity One
MetaboAnalyst

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