Document Detail


Oxidized low density lipoprotein suppresses expression of inducible cyclooxygenase in human macrophages.
MedLine Citation:
PMID:  10397690     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Atherogenesis involves several aspects of chronic inflammation and wound healing. Indeed, the atheroma is considered a special case of tissue response to injury. Injurious stimuli may include lipoproteins trapped within lesions where protein and lipid moieties have undergone chemical modifications. We have studied the effect of oxidized low density lipoproteins (ox-LDL) on inducible cyclooxygenase (Cox-2) in human monocyte-derived macrophages exposed to bacterial lipopolysaccharide (LPS). Levels of both Cox-2 and constitutive cyclooxygenase (Cox-1) were assessed using Western blot analysis. Prior incubation of macrophages with ox-LDL resulted in a strong inhibition of Cox-2 induced by LPS, without effect on Cox-1. The inhibitory effect was dependent on ox-LDL concentration and its onset was early in time (already detectable 1 hour after macrophage exposure to ox-LDL). Native LDL, and other forms of modified LDL, were without effect. The inhibition was dependent on endocytosis of ox-LDL and could be reproduced using the lipid extract from ox-LDL. Lysophosphatidylcholine, 7beta-hydroxycholesterol, and 7-oxocholesterol failed to mimic the inhibition, but oxidized arachidonic acid-containing phospholipids, produced by autoxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, markedly inhibited Cox-2. The observation that ox-LDL downregulates Cox-2 in human macrophages may explain the fact that, within atheromata, the transformation of macrophages into foam cells results in attenuation of the inflammatory response, thus contributing to progression of atherogenesis.
Authors:
S Eligini; S Colli; F Basso; L Sironi; E Tremoli
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  19     ISSN:  1079-5642     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-07-29     Completed Date:  1999-07-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1719-25     Citation Subset:  IM    
Affiliation:
E. Grossi Paoletti Center, Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy.
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Endocytosis
Humans
Lipopolysaccharides / pharmacology
Lipoproteins / metabolism
Lipoproteins, LDL / pharmacology*
Lipoxygenase / biosynthesis,  drug effects*
Lysosomes / metabolism
Macrophage Colony-Stimulating Factor / physiology
Macrophages / enzymology*
Chemical
Reg. No./Substance:
0/Lipopolysaccharides; 0/Lipoproteins; 0/Lipoproteins, LDL; 0/oxidized low density lipoprotein; 81627-83-0/Macrophage Colony-Stimulating Factor; EC 1.13.11.12/Lipoxygenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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