Inhibitory effect of PPAR-gamma activator on IL-6 and mPGES protein expression in PBMC induced by homocysteine

Hemodial Int. 2005 Oct:9 Suppl 1:S15-20. doi: 10.1111/j.1542-4758.2005.01165.x.

Abstract

The objective was to investigate the relationship between homocysteine (HCY), peroxisome proliferator-activated receptors (PPAR)-gamma and the expression of interleukin 6 (IL-6) and microsomal prostaglandin E synthase (mPGES) by peripheral blood mononuclear cell (PBMC) culture in vitro, as well as to look at the intervention with HCY and PPAR-gamma activators (troglitazone and rosiglitazone). PBMC were isolated from venous blood of normal volunteers and incubated with HCY and PPAR-gamma activator of varying concentrations for 24 hr. The supernatant of the culture medium was collected in order to determine the IL-6 and mPGES levels by ELISA assay. The results show that the expression of IL-6 and mPGES in the HCY experimental group was significantly higher than that in the control group (p<0.01 and p<0.05, respectively). Additionally, the IL-6 and mPGES levels rose with the increase of HCY in a dose-dependent manner (p<0.01 and p<0.05, respectively). PPAR-gamma activator could significantly inhibit the increase of IL-6 and mPGES induced by 100 micromol/L HCY (p<0.05 and p<0.01, respectively). In conclusion, HCY can increase the expression of IL-6 and mPGES, while PPAR-gamma activator can inhibit the increase of IL-6 and mPGES induced by HCY.

MeSH terms

  • Cells, Cultured
  • Chromans / pharmacology*
  • Dose-Response Relationship, Drug
  • Homocysteine / pharmacology*
  • Humans
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / pharmacology
  • Intramolecular Oxidoreductases / biosynthesis*
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / therapy
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / enzymology
  • Leukocytes, Mononuclear / metabolism
  • Microsomes / enzymology
  • PPAR gamma / drug effects
  • PPAR gamma / metabolism*
  • Prostaglandin-E Synthases
  • Renal Dialysis
  • Rosiglitazone
  • Thiazolidinediones / pharmacology*
  • Troglitazone

Substances

  • Chromans
  • Interleukin-6
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • Homocysteine
  • Intramolecular Oxidoreductases
  • Prostaglandin-E Synthases
  • Troglitazone