Prostaglandin J(2) inhibition of mesangial cell iNOS expression

Clin Immunol. 2001 Mar;98(3):337-45. doi: 10.1006/clim.2000.4985.

Abstract

Mesangial cells from MRL/lpr mice, a model of lupus, overproduce nitric oxide (NO) compared to controls. J series prostaglandins (PG) and thiazolidinediones block LPS stimulation of NO production via the activation of peroxisome proliferator-activator receptor-gamma (PPAR-gamma) in macrophages but utilize an alternative mechanism in microglial cells. We investigated the mechanism by which PGJ(2) inhibits NO production in LPS/IFN-gamma-stimulated MRL/lpr mesangial cells. Our results demonstrated that LPS/IFN-gamma addition to MRL/lpr mesangial cells stimulated iNOS activation, expression of p-38 kinase and p44/42 MAPK, and NF-kappaB translocation to the nucleus. Both pioglitazone, a specific PPAR-gamma agonist, and PGJ(2) blocked NO production, iNOS protein expression, and iNOS mRNA transcription. PGJ(2) failed to inhibit nuclear NF-kappaB translocation or p44/42 MAPK or p-38 kinase induction in stimulated mesangial cells. These data suggest that PGJ(2) blocks iNOS expression and subsequent NO production in mesangial cells via a PPAR-gamma-mediated mechanism either by interfering with NF-kappaB transcriptional activity or by an NF-kappaB-independent mechanism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Glomerular Mesangium / enzymology*
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred MRL lpr
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II
  • Phosphorylation
  • Prostaglandin D2 / analogs & derivatives*
  • Prostaglandin D2 / pharmacology*
  • Receptors, Cytoplasmic and Nuclear / analysis
  • Transcription Factors / analysis

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • 9-deoxy-delta-9-prostaglandin D2
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Mitogen-Activated Protein Kinases
  • Prostaglandin D2