Oxidized low-density lipoproteins may induce expression of monocyte chemotactic protein-3 in atherosclerotic plaques

• Published in: Biochemical and biophysical research communications 2004-10, Vol.323 (3), p.898-905
• Main Authors: Jang, Moon Kyoo, Kim, Ji Young, Jeoung, Nam Ho, Kang, Mi Ae, Choi, Myung-Sook, Oh, Goo Taeg, Nam, Kyung Tak, Lee, Won-Ha, Park, Yong Bok
• Format: Article
• Language: English
• Subjects: Atherosclerosis; Carotid Arteries - drug effects; Carotid Arteries - metabolism; Carotid Arteries - pathology; Chemokine CCL7; Coronary Artery Disease - metabolism; Coronary Artery Disease - pathology; Cytokines - metabolism; Dose-Response Relationship, Drug; Gene Expression Regulation - drug effects; Humans; Lipoproteins, LDL - metabolism; Lipoproteins, LDL - pharmacology; MCP-3; Monocyte Chemoattractant Proteins - metabolism; Monocyte/macrophage; Monocytes - drug effects; Monocytes - metabolism; Monocytes - pathology; Oxidation-Reduction; Oxidized LDL; PPARγ; Tissue Distribution; U937 Cells
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.08.178

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 γ (PPARγ). Introduction of an endogenous PPARγ 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 PPARγ. These results suggest that oxLDL delivers its signal for MCP-3 expression via PPARγ, which may be further related to the atherogenesis.