Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques.
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.
Jang
Moon Kyoo
MK
Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-2753, USA.
Kim
Ji Young
JY
Jeoung
Nam Ho
NH
Kang
Mi Ae
MA
Choi
Myung-Sook
MS
Oh
Goo Taeg
GT
Nam
Kyung Tak
KT
Lee
Won-Ha
WH
Park
Yong Bok
YB
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
C515450:CCL7 protein, human; D054410:Chemokine CCL7; D016207:Cytokines; D008077:Lipoproteins, LDL; D018945:Monocyte Chemoattractant Proteins