| Oxidized phospholipids are more potent antagonists of lipopolysaccharide than inducers of inflammation. | |
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MedLine Citation:
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PMID: 21068406 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Polyunsaturated fatty acids are precursors of multiple pro- and anti-inflammatory molecules generated by enzymatic stereospecific and positionally specific insertion of oxygen, which is a prerequisite for recognition of these mediators by cellular receptors. However, nonenzymatically oxidized free and esterified polyunsaturated fatty acids also demonstrate activities relevant to inflammation. In particular, phospholipids containing oxidized fatty acid residues (oxidized phospholipids; OxPLs) were shown to induce proinflammatory changes in endothelial cells but paradoxically also to inhibit inflammation induced via TLR4. In this study, we show that half-maximal inhibition of LPS-induced elevation of E-selectin mRNA in endothelial cells developed at concentrations of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (OxPAPC) 10-fold lower than those required to induce proinflammatory response. Similar concentration difference was observed for other classes and molecular species of OxPLs. Upon injection into mice, OxPAPC did not elevate plasma levels of IL-6 and keratinocyte chemoattractant but strongly inhibited LPS-induced upregulation of these inflammatory cytokines. Thus, both in vitro and in vivo, anti-LPS effects of OxPLs are observed at lower concentrations than those required for their proinflammatory action. Quantification of the most abundant oxidized phosphatidylcholines by HPLC/tandem mass spectrometry showed that circulating concentrations of total oxidized phosphatidylcholine species are close to the range where they demonstrate anti-LPS activity but significantly lower than that required for induction of inflammation. We hypothesize that low levels of OxPLs in circulation serve mostly anti-LPS function and protect from excessive systemic response to TLR4 ligands, whereas proinflammatory effects of OxPLs are more likely to develop locally at sites of tissue deposition of OxPLs (e.g., in atherosclerotic vessels). |
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Authors:
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Olga V Oskolkova; Taras Afonyushkin; Beatrix Preinerstorfer; Wolfgang Bicker; Elena von Schlieffen; Eva Hainzl; Svitlana Demyanets; Gernot Schabbauer; Wolfgang Lindner; Alexandros D Tselepis; Johann Wojta; Bernd R Binder; Valery N Bochkov |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-11-10 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-03 Completed Date: 2011-01-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 7706-12 Citation Subset: AIM; IM |
Affiliation:
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Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cytokines / biosynthesis, immunology E-Selectin / biosynthesis, immunology Female Inflammation / chemically induced, immunology*, metabolism Inflammation Mediators / immunology, metabolism Lipopolysaccharides / toxicity* Mice Phosphatidylcholines / immunology, metabolism, pharmacology* RNA, Messenger / biosynthesis, immunology Toll-Like Receptor 4 / agonists, immunology*, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/E-Selectin; 0/Inflammation Mediators; 0/Lipopolysaccharides; 0/Phosphatidylcholines; 0/RNA, Messenger; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 0/lipopolysaccharide, Escherichia coli 0111 B4; 0/oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine |
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