Research Paper Volume 11, Issue 24 pp 12810—12821
Nicotine instigates podocyte injury via NLRP3 inflammasomes activation
- 1 Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA
Received: August 7, 2019 Accepted: December 5, 2019 Published: December 13, 2019https://doi.org/10.18632/aging.102611
How to Cite
Copyright © 2019 Singh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background/Aims: Recent studies have shown that nicotine induces podocyte damage. However, it remains unknown how nicotine induces podocyte injury. The present study tested whether nicotine induces NLRP3 inflammasomes activation and thereby contributes to podocyte injury.
Results: Nicotine treatment significantly increased the colocalization of NLRP3 with Asc, caspase-1 activity, IL-β production, cell permeability in podocytes compared to control cells. Pretreatment with caspase-1 inhibitor, WEHD significantly abolished the nicotine-induced colocalization of NLRP3 with Asc, caspase-1 activity, IL-1β production and cell permeability in podocytes. Immunofluorescence analysis showed that nicotine treatment significantly decreased the podocin and nephrin expression compared to control cells. However, prior treatment with WEHD attenuated the nicotine-induced podocin and nephrin reduction. In addition, we found that nicotine treatment significantly increased the O2.- production compared to control cells. However, prior treatment with WEHD did not alter the nicotine-induced O2.- production. Furthermore, prior treatment with ROS scavenger, NAC significantly attenuated the nicotine-induced caspase-1 activity, IL-1β production, podocin and nephrin reduction in podocytes.
Conclusions: Nicotine-induced the NLRP3 inflammasome activation in podocytes and thereby results in podocyte injury.
Methods: Inflammasome formation and immunofluorescence expressions were quantified by confocal microscopy. Caspase-1 activity, IL-1β production and O2.- production were measured by ELISA and ESR.