Prostaglandin J2 Inhibition of Mesangial Cell iNOS Expression

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-γ (PPAR-γ) in macrophages but utilize an alternative mechanism in microglial cells. We investigated the mechanism by which PGJ 2 inhibits NO production in LPS/IFN-γ-stimulated MRL/lpr mesangial cells. Our results demonstrated that LPS/IFN-γ addition to MRL/lpr mesangial cells stimulated iNOS activation, expression of p-38 kinase and p44/42 MAPK, and NF-κB translocation to the nucleus. Both pioglitazone, a specific PPAR-γ agonist, and PGJ 2 blocked NO production, iNOS protein expression, and iNOS mRNA transcription. PGJ 2 failed to inhibit nuclear NF-κB 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-γ-mediated mechanism either by interfering with NF-κB transcriptional activity or by an NF-κB-independent mechanism.