Suppression of experimental crescentic glomerulonephritis by peroxisome proliferator-activated receptor (PPAR) γ activators

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It has been recently reported that peroxisome proliferator-activated receptor (PPAR) γ exhibits anti-inflammatory effects. A couple of reports suggests effects of PPAR γon kidney cells, but precise knowledge are limited.First, we examined the effects of PPARg activators on the apoptosis of clonal kidney cells (LLC-PK1), RT-PCR revealed the expression of PPARg in LLC-PK1 cells. The ligands for PPARg such as troglitazone, BRL49653 and 15-deoxy-delta-12,14-prostaglandin J2 inhibited serum-deprivation-induced apoptosis of the cells. PPARa activators did not mimic the effect of troglitazone. Antiapoptotic effects of troglitazone were partially blocked by a phosphatidyl-inositol-3 kinase (PI3K) inhibitor, wortmannin, but not by other kinase inhibitors. Further, we showed that troglitazone increased the expression of c-myc which was reported to cause apoptosis in the absence of serum in other systems. However, the expression of bcl-2 was not affected. These results suggest that the activation … More of PPARg has an inhibitory effect on the apoptosis induced by serum deprivation through the PI3K pathway in LLC-PK1 cells.Secondary, crescentic glomerulonephritis was induced by the injection of rabbit anti-rat glomerular basement membrane antibody in WKY rats. Administration of troglitazone suppressed urinary protein excretion and crescent formation as indicated by crescent scores. Pioglitazone mimicked the effect of troglitazone, but PPAR α-activators did not. Immunohistology revealed that troglitazone and pioglitazone inhibited the infiltration of ED-1-positive monocyte/macrophages and CD8-positive cells into glomeruli. In the present study, we demonstrated that PPAR γ activators exert antinephritic effects by suppressing the recruitment of inflammatory cells via PPARg-dependent mechanism.In conclusion, in kidney cells, PPAR γ-activators inhibits apoptosis of cultured kidney cells in vitro and suppresses experimental glomerulonephritis in rats, PPARγ-dependent mechanism may have a important role in kidney cells. Less