Isolevuglandin-type lipid aldehydes induce the inflammatory response of macrophages by modifying phosphatidylethanolamines and activating the receptor for advanced glycation endproducts

Antioxidants & Redox Signaling
Lilu GuoSean S Davies

Abstract

Increased lipid peroxidation occurs in many conditions associated with inflammation. Because lipid peroxidation produces lipid aldehydes that can induce inflammatory responses through unknown mechanisms, elucidating these mechanisms may lead to development of better treatments for inflammatory diseases. We recently demonstrated that exposure of cultured cells to lipid aldehydes such as isolevuglandins (IsoLG) results in the modification of phosphatidylethanolamine (PE). We therefore sought to determine (i) whether PE modification by isolevuglandins (IsoLG-PE) occurred in vivo, (ii) whether IsoLG-PE stimulated the inflammatory responses of macrophages, and (iii) the identity of receptors mediating the inflammatory effects of IsoLG-PE. IsoLG-PE levels were elevated in plasma of patients with familial hypercholesterolemia and in the livers of mice fed a high-fat diet to induce obesity and hepatosteatosis. IsoLG-PE potently stimulated nuclear factor kappa B (NFκB) activation and expression of inflammatory cytokines in macrophages. The effects of IsoLG-PE were blocked by the soluble form of the receptor for advanced glycation endproducts (sRAGE) and by RAGE antagonists. Furthermore, macrophages derived from the bone marrow of Ager n...Continue Reading

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Citations

Mar 26, 2016·Free Radical Biology & Medicine·Andrea AnnibalMaria Fedorova
Sep 12, 2015·Critical Reviews in Food Science and Nutrition·Tamara Y Forbes-HernandezMaurizio Battino
May 10, 2019·Journal of Leukocyte Biology·Yulia Y TyurinaValerian E Kagan
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Oct 11, 2017·Current Pharmacology Reports·Sean S Davies, Linda S Zhang
Jul 10, 2020·Antioxidants & Redox Signaling·Erica GianazzaCristina Banfi
Dec 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elena E Pohl, Olga Jovanovic
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Jul 1, 2020·Obesity Research & Clinical Practice·Sudipa SarkarCharles Robb Flynn
Oct 26, 2020·Free Radical Biology & Medicine·Michael AschnerAlexey A Tinkov

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Methods Mentioned

BETA
PCR
ELISA
transgenic
NMR
transfection
Assay

Software Mentioned

GraphPad Prism
Xcaliber
GraphPad

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