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

Moon Kyoo Jang, Ji Young Kim, Nam Ho Jeoung, Mi Ae Kang, Myung Sook Choi, Goo Taeg Oh, Kyung Tak Nam, Won Ha Lee, Yong Bok Park

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)898-905
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume323
Issue number3
DOIs
StatePublished - 22 Oct 2004

Keywords

  • Atherosclerosis
  • MCP-3
  • Monocyte/macrophage
  • Oxidized LDL
  • PPARγ

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