Oxidized low density lipoproteins downregulate LPS-induced platelet-activating factor receptor expression in human monocyte-derived macrophages: implications for LPS-induced nuclear factor-kappaB binding activity

Eur J Biochem. 2001 Aug;268(16):4489-96. doi: 10.1046/j.1432-1327.2001.02372.x.

Abstract

Monocytes/macrophages play a key role in atherogenesis due to their inflammatory properties including formation of lipid mediators such as platelet-activating-factor (PAF). We investigated the effect of oxidized low-density lipoprotein (oxLDL) on lipopolysaccharide (LPS)-induced PAF receptor (PAF-R) expression in human macrophages and the implication of the nuclear factor (NF)-kappaB in this regulation. LPS-treatment (1 microg.mL(-1)) of macrophages increased PAF binding and PAF-R mRNA expression by 56% (P < 0.05) and twofold (P < 0.01), respectively. In contrast, highly oxidized low-density lipoprotein [ox24hLDL; 100 microg.mL(-1); thiobarbituric acid reacting substances: 31 +/- 3 nmol equiv. malondialdehyde (MDA).mg protein LDL-1] diminished PAF-R expression (-69%; P < 0.05) and mRNA level (- 45%; P < 0.01). LPS pretreatment induced the activated form of p65 in the nuclear compartment of macrophages (detected by Western blotting) and NF-kappaB binding activity (by electrophoretic mobility shift assay). Treatment of macrophages with ox24hLDL suppressed the LPS-induced binding of NF-kappaB to DNA. In addition, treatment of macrophages with lysophosphatidylcholine (2 and 10 microM), a major component of oxLDL, inhibited the LPS-induced NF-kappaB binding to DNA and reduced PAF binding by 30 and 70%, respectively. In conclusion, oxLDL may downregulate PAF-R expression in human macrophages by inhibiting LPS-induced NF-kappaB binding to DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteriosclerosis / etiology
  • DNA / metabolism
  • Down-Regulation
  • Humans
  • Lipopolysaccharides / pharmacology*
  • Lipoproteins, LDL / pharmacology*
  • Lysophosphatidylcholines / pharmacology
  • Macrophages / chemistry
  • Macrophages / drug effects*
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • NF-kappa B / metabolism*
  • Platelet Activating Factor / metabolism
  • Platelet Membrane Glycoproteins / drug effects*
  • Receptors, Cell Surface*
  • Receptors, G-Protein-Coupled*

Substances

  • Lipopolysaccharides
  • Lipoproteins, LDL
  • Lysophosphatidylcholines
  • NF-kappa B
  • Platelet Activating Factor
  • Platelet Membrane Glycoproteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • oxidized low density lipoprotein
  • platelet activating factor receptor
  • DNA