Anti-inflammatory effect of PPARγ in cultured human mesangial cells

Our aim is to investigate whether peroxisome proliferator-activator receptor-γ (PPARγ) expression was altered in human mesangial cells under inflammatory stress and whether PPARγ could retard the inflammatory responses. Based on cultured human mesangial cell lines (HMCLs), PPARγ expressions at protein and mRNA levels were observed by Western blot analysis and reverse transcriptase polymerase chain reaction. Informatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Our results demonstrated that PPARγ protein expression was dramatically increased in HMCLs stimulated by IL-1β (10 ng/mL). The levels of IL-6 and TNF-α in HMCL supernatants, protein, and mRNA expressions of PPARγ in IL-1β challenge cells were significantly increased more than those in untreated cells. Importantly, PPARγ agonists troglitazone, rosiglitazone, and 15-deoxy-Δ ^12,14-prosglandin J₂ significantly decreased the up expression of TNF-α and IL-6 in HMCL supernatants stimulated by IL-1β. Furthermore, troglitazone downregulated TNF-α and IL-6 mRNA expression from IL-1β challenge HMCLs. Our data suggest that PPARγ plays an important role in mesangial cells responding to inflammatory stress. PPARγ may prove to be a pharmacological target in glomerulonephritis.