NLRP3 Inflammasome as a Novel Target to Abrogate NicotineInduced Podocyte Injury
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abstract
Recent in vivo and in vitro studies have established the role of nicotine in chronic kidney diseases. However, the molecular mechanisms of how nicotine induces chronic kidney disease are still unclear. The present study tested whether nicotine induces NLRP3 inflammasome formation and activation and thereby contributes to podocyte injury and dysfunction. Confocal microscopic analysis showed that nicotine treatment increased the colocalization of NLRP3 with Asc in podocytes compared to control cells. Pretreatment with caspase1 inhibitor, WEHD abolished the nicotineinduced colocalization of NLRP3 with Asc, suggesting the formation of Nlrp3 inflammasomes. Correspondingly, nicotine treatment significantly increased the caspase1 activity and IL1 production compared to control cells. The prior treatment with WEHD significantly attenuated the nicotineinduced caspase1 activity and IL1 production. Immunofluorescence analysis showed that nicotine treatment significantly decreased the podocin and nephrin expression compared to control cells. However, prior treatment with WEHD attenuated the nicotineinduced podocin and nephrin reduction. In addition, prior treatment with ROS inhibitor, NAC significantly attenuated the nicotineinduced caspase1 activity, IL1 production and podocin and nephrin reduction in podocytes. Based on these results, it is concluded that nicotineinduced the NLRP3 inflammasome activation in podocytes and thereby resulting in podocyte injury and dysfunction (supported by NIH grant, DK104031).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
