title: Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques.
abstract: Genes induced or suppressed by oxidized low-density lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using the differential display reverse transcriptase polymerase chain reaction. One of the differentially expressed (up-regulated) cDNA fragments was found to contain sequences corresponding to monocyte chemotactic protein-3 (MCP-3). The stimulatory effect of the oxLDL on the expression of MCP-3 mRNA was both time- and dose-dependent. Treatment with GF109203X and genistein, inhibitors of protein kinase C and tyrosine kinase, respectively, had no effect on the induction of MCP-3 mRNA by oxLDL, while treatment with cycloheximide inhibited the induction. The induction was reproduced by the lipid components in oxLDL such as 9-HODE and 13-HODE, which are known to activate the peroxisome proliferator-activated receptor gamma (PPARgamma). Introduction of an endogenous PPARgamma ligand, 15d-PGJ2, in the culture of THP-1 cells resulted in the induction of MCP-3 gene expression. Furthermore, analyses of human atherosclerotic plaques revealed that the expressional pattern of MCP-3 in the regions of neointimal and necrotic core overlapped with that of PPARgamma. These results suggest that oxLDL delivers its signal for MCP-3 expression via PPARgamma, which may be further related to the atherogenesis.
authors.affiliation: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-2753, USA.
authors.forename: Moon Kyoo
authors.initials: MK
authors.lastname: Jang
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Nam Ho
authors.initials: NH
authors.lastname: Jeoung
authors.forename: Mi Ae
authors.initials: MA
authors.lastname: Kang
authors.forename: Myung-Sook
authors.initials: MS
authors.lastname: Choi
authors.forename: Goo Taeg
authors.initials: GT
authors.lastname: Oh
authors.forename: Kyung Tak
authors.initials: KT
authors.lastname: Nam
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Park
mesh_terms: D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D054410:Chemokine CCL7; D003324:Coronary Artery Disease / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology*; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010084:Oxidation-Reduction; D014018:Tissue Distribution; D020298:U937 Cells
chemical_list: C515450:CCL7 protein, human; D054410:Chemokine CCL7; D016207:Cytokines; D008077:Lipoproteins, LDL; D018945:Monocyte Chemoattractant Proteins