Prostaglandin J(2) inhibition of mesangial cell iNOS expression

Mesangial cells from MRL/lpr mice, a model of lupus, overproduce nitric oxi de (NO) compared to controls. J series prostaglandins (PG) and thiazolidine diones block LPS stimulation of NO production via the activation of peroxis ome proliferator-activator receptor-gamma (PPAR-gamma) in macrophages but u tilize an alternative mechanism in microglial cells. We investigated the me chanism by which PGJ(2) inhibits NO production in LPS/IFN-gamma -stimulated MRL/lpr mesangial cells. Our results demonstrated that LPS/IFN-gamma addit ion to MRL/lpr mesangial cells stimulated MOS activation, expression of p-3 8 kinase and p44/42 MAPK, and NF-kappaB translocation to the nucleus. Both pioglitazone, a specific PPAR-gamma agonist, and PGJ(2) blocked NO producti on, iNOS protein expression, and iNOS mRNA transcription. PGJ(2) failed to inhibit nuclear NF-kappaB translocation or p44/42 MAPK or p-38 kinase induc tion in stimulated mesangial cells. These data suggest that PGJ(2) blocks i NOS expression and subsequent NO production in mesangial cells via a PPAR-g amma -mediated mechanism either by interfering with NF-kappaB transcription al activity or by an NF-kappaB-independent mechanism. (C) 2001 Academic Pre ss.