Activators of peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit inducible nitric oxide synthase expression but increase heme oxygenase-1 expression in rat glial cells

Neurosci Lett. 1999 Mar 5;262(2):129-32. doi: 10.1016/s0304-3940(99)00055-5.

Abstract

The peroxisome proliferator-activated receptor-gamma (PPARgamma) is activated by 15-deoxy-delta(12,14) prostaglandin J2 (15d-PGJ2), anti-diabetic thiazolidinediones and several non-steroidal anti-inflammatory drugs (NSAIDs). In rat glial cells, lipopolysaccharide and interferon-gamma (LPS/IFN-gamma) induced expression of both inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). PPARgamma activators inhibited iNOS expression by LPS and IFN-gamma. However, PPARgamma activator alone induced HO-1 expression and further enhanced LPS/IFN-gamma-induced HO-1 expression. These results suggest that activation of PPARgamma negatively regulate iNOS expression and positively regulates HO-1 expression in glial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alitretinoin
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Brain / cytology
  • Cells, Cultured
  • Dinoprostone / pharmacology
  • Enzyme Induction / drug effects
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Heme Oxygenase (Decyclizing) / biosynthesis*
  • Heme Oxygenase-1
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Neuroglia / cytology
  • Neuroglia / drug effects
  • Neuroglia / enzymology*
  • Neuroglia / metabolism
  • Nitric Oxide Synthase / biosynthesis*
  • Nitric Oxide Synthase Type II
  • Nitrites / metabolism
  • Prostaglandin D2 / analogs & derivatives
  • Prostaglandin D2 / pharmacology
  • Pyrimidines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Transcription Factors / agonists*
  • Tretinoin / pharmacology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipopolysaccharides
  • Nitrites
  • Pyrimidines
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Thiazolidinediones
  • Transcription Factors
  • Alitretinoin
  • Tretinoin
  • Interferon-gamma
  • pirinixic acid
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Dinoprostone
  • Prostaglandin D2
  • ciglitazone