Peroxisome proliferator-activated receptor gamma prevents the production of NOD-like receptor family, pyrin domain containing 3 inflammasome and interleukin 1 beta in HK-2 renal tubular epithelial cells stimulated by monosodium urate crystals

Recent evidence showed that peroxisome proliferator-activated receptor gamma (PPAR gamma) ameliorates a variety of inflammatory conditions. The present study aimed to investigate the role of PPAR gamma in regulating NOD-like receptor family, pyrin domain containing 3 (NALP3) inflammasome and interleukin (IL)-1 beta levels during monosodium urate (MSU) crystal-induced inflammation. HK-2 cells were incubated with or without 200 mu g/ml MSU crystals, and mRNA and protein levels of PPAR gamma were determined using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. To verify the role of PPAR gamma, HK-2 cells were pre-treated with PPAR gamma agonist pioglitazone, and the levels of NALP3 inflammasome and IL-1 beta were detected by western blot analysis and ELISA. The results showed that MSU crystals increased PPAR gamma expression in HK-2 cells at 24 h, while the expression decreased to normal levels at 48 h. It was also demonstrated that although the PPAR gamma agonist pioglitazone did not alter the mRNA and protein levels of PPAR gamma, it significantly reduced the MSU crystal-induced production of NALP3 inflammasome and IL-1 beta in HK-2 cells, possibly by increasing the level of PPAR gamma activity. In conclusion, the results of the present study indicated that PPAR gamma prevented NALP3 inflammasome formation and IL-1 beta production in HK-2 cells stimulated by MSU crystals, which indicated that PPAR gamma may represent a novel target for the treatment of hyperuricemic nephropathy.