Endoplasmic Reticulum Stress Is Involved In Angiotensin Ⅱ Induced NLRP3 Inflammasome Activation In Renal Proximal Tubular Cells

Aims:Previous studies have demonstrated that angiotensin Ⅱ (Ang Ⅱ) plays an important role in tubulointerstitial inflammation. This study investigated whether endoplasmic reticulum stress (ERS) is involved in Ang Ⅱ induced NLRP3 inflammasome activation.Methods:All experiments were performed by using of the HK-2 cells. The gene and protein expression levels of molecules involved in the NLRP3 inflammasome and ERS were examined by real-time PCR, western blot, and immunofluorescence.Results:After treatment with Ang Ⅱ, the mRNA and protein expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 increased in a dose-and time-dependent manner with peaks at 100nM and 12 h. However, pretreatment with telmisartan could significantly reduce the mRNA and protein expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18. In addition, immunofluorescence studies showed that Ang Ⅱ could increase the expression of NLRP3 and ASC, while telmisartan reduced their expression. Similarly, the mRNA and protein expression of GRP78 and p-eIF2a were increased in a dose- and time-dependent manner, but 4-PBA could significantly inhibit the mRNA and protein expression of NLRP3, ASC, caspase-1, IL-1β, and IL-18.Conclusion:Our findings demonstrate that Ang Ⅱ induced inflammasome activation in HK-2 cells, and ER stress may be involved in this process. These findings may represent a newly identified mechanism for the renal RAS system to induce tubulointerstitial inflammation.