The Expression Of PPARγ And The Effect Of Pioglitazone On The Production Of And NALP3Inflammasome And IL-1β In Uric Acid-stimulated Renal Tubular Epithelial Cells (HK-2Cells)

Background/Aims Peroxisome proliferator-activated receptory(PPARy) is a member of the nuclear hormone receptor superfamily. Recent evidence shows that PPARyameliorates a variety of inflammatory conditions.IL-1β、NALP3inflammasome play a pivotal role in the inflammatory response, which was induced by hyperuricemia. This study was undertaken to investigate the PPARyexpression by hyperuricemia-stimulated HK-2cells and evaluate the role of PPARy agonists pioglitazone in regulating IL-1β、NALP3inflammasome expression during the uric acid-induced inflammation.Methods HK-2cells were incubated with or without uric acid at concentration of200ug/ml. PPARyexpression of HK-2cells was determined by reverse transcription polymerase chain reaction (RT-PCR) and western blots. To investigate the effects of pioglitazone in vitro on uric acid-induced cytokine production, HK-2cells were pretreated with PPARyagonist pioglitazone.The IL-1β、NALP3inflammasome level were also determined by RT-PCR and western blots.Results Hyperuricemia increased PPARyexpression in HK-2cells at early time, later it decreased at the normal level. High gene expression was observed at4hours after stimulation, increased PPARyprotein was observed at24hours after stimulation. We also demonstrated that the PPARyagonist pioglitazone can not altered PPARymRNA and protein level.But a PPARyligand pioglitazone significantly reduced the uric acid-induced production of IL-1β、NALP3inflammasome on HK-2cell, therefore, we can concluded that Pioglitazone may enhance the activity of PPARγwhile not increase the transcription, this enhanced activity of PPARγameliorated the inflammation induced by hyperuricemia.Conclusions Uric acid rapidly and selectively induced PPARy expression by renal tubular epithelial cells. Pioglitazone significantly decreased IL-1β、NALP3inflammasome expression in HK-2cells after stimulated by uric acid, which were may mediated by PPARy-dependent pathways. These results point to PPARyas a remarkable new target in the improvement of hyperuricemia nephropathy.