title: Oxidized LDLs inhibit TLR-induced IL-10 production by monocytes: a new aspect of pathogen-accelerated atherosclerosis.
abstract: It is widely accepted that oxidized low-density lipoproteins and local infections or endotoxins in circulation contribute to chronic inflammatory process at all stages of atherosclerosis. The hallmark cells of atherosclerotic lesions-monocytes and macrophages-are able to detect and integrate complex signals derived from lipoproteins and pathogens, and respond with a spectrum of immunoregulatory cytokines. In this study, we show strong inhibitory effect of oxLDLs on anti-inflammatory interleukin-10 production by monocytes responding to TLR2 and TLR4 ligands. In contrast, pro-inflammatory tumor necrosis factor secretion was even slightly increased, when stimulated with lipopolysaccharide from Porphyromonas gingivalis-an oral pathogen associated with atherosclerosis. The oxLDLs modulatory activity may be explained by altered recognition of pathogen-associated molecular patterns, which involves serum proteins, particularly vitronectin. We also suggest an interaction between vitronectin receptor, CD11b, and TLR2. The presented data support a novel pathway for pathogen-accelerated atherosclerosis, which relies on oxidized low-density lipoprotein-mediated modulation of anti-inflammatory response to TLR ligands.
authors.affiliation: Department of Immunology, Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Bzowska
authors.forename: Anna
authors.initials: A
authors.lastname: Nogieć
authors.forename: Joanna
authors.initials: J
authors.lastname: Skrzeczyńska-Moncznik
authors.forename: Barbara
authors.initials: B
authors.lastname: Mickowska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Guzik
authors.forename: Juliusz
authors.initials: J
authors.lastname: Pryjma
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D018955:CD36 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000276:immunology; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis*; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018955:CD36 Antigens; D039302:Integrin alphaVbeta3; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008077:Lipoproteins, LDL; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D019096:Vitronectin; C082161:lipopolysaccharide A; C099252:oxidized low density lipoprotein; D016753:Interleukin-10