Advanced Glycated apoA-IV Loses Its Ability to Prevent the LPS-Induced Reduction in Cholesterol Efflux-Related Gene Expression in Macrophages. (14th January 2020)

• Record Type: Journal Article
• Authors: Shimabukuro Okuda, Ligia; Tallada Iborra, Rodrigo; Ramos Pinto, Paula; Fabres Machado, Ubiratan; Corrêa-Giannella, Maria Lucia; Pickford, Russell; Woods, Tom; Brimble, Margaret Anne; Rye, Kerry-Anne; Passarelli, Marisa
• Other Names: Hatanaka Elaine Academic Editor.
• Is Part Of: Mediators of inflammation. Volume 2020(2020)
• Publication Date: 2020-01-14
• Subjects: Inflammation -- Mediators -- Periodicals; Biological response modifiers -- Periodicals; Inflammation (Pathologie) -- Médiateurs; Immunomodulateurs; Biological response modifiers; Inflammation -- Mediators; Immunology; Autacoids; Immunologic Factors; Cell Adhesion Molecules; Cell Communication; Cytokines; Inflammation; Periodicals; Electronic journals; 616.0473
• DOI: 10.1155/2020/6515401
• Languages: English
• ISSNs: 0962-9351

Abstract

Abstract : We addressed how advanced glycation (AGE) affects the ability of apoA-IV to impair inflammation and restore the expression of genes involved in cholesterol efflux in lipopolysaccharide- (LPS-) treated macrophages. Recombinant human apoA-IV was nonenzymatically glycated by incubation with glycolaldehyde (GAD), incubated with cholesterol-loaded bone marrow-derived macrophages (BMDMs), and then stimulated with LPS prior to measurement of proinflammatory cytokines by ELISA. Genes involved in cholesterol efflux were quantified by RT-qPCR, and cholesterol efflux was measured by liquid scintillation counting. Carboxymethyllysine (CML) and pyrraline (PYR) levels, determined by Liquid Chromatography-Mass Spectrometry (LC-MS/MS), were greater in AGE-modified apoA-IV (AGE-apoA-IV) compared to unmodified-apoA-IV. AGE-apoA-IV inhibited expression of interleukin 6 ( Il6 ), TNF-alpha ( Tnf ), IL-1 beta ( Il1b ), toll-like receptor 4 ( Tlr4 ), tumor necrosis factor receptor-associated factor 6 ( Traf6 ), Janus kinase 2/signal transducer and activator of transcription 3 ( Jak2/Stat3 ), nuclear factor kappa B ( Nfkb ), and AGE receptor 1 ( Ddost ) as well as IL-6 and TNF-alpha secretion. AGE-apoA-IV alone did not change cholesterol efflux or ABCA-1 levels but was unable to restore the LPS-induced reduction in expression of Abca1 and Abcg1 . AGE-apoA-IV inhibited inflammation but lost its ability to counteract the LPS-induced changes in expression of genes involved in macrophage cholesterol efflux that may contribute to atherosclerosis.