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NLRP3 Inflammasome as a Novel Target to Abrogate Nicotine‐Induced Podocyte Injury
Author(s) -
Singh Gurinder Bir,
Kshirasagar Naresh,
Patibandla Sai,
Hussain Tahir,
Li Xiang,
Li PinLan,
Koka Saisudha,
Boini Krishna M
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.749.5
Subject(s) - nephrin , podocin , inflammasome , podocyte , nicotine , pharmacology , chemistry , in vivo , colocalization , medicine , microbiology and biotechnology , kidney , biology , inflammation , proteinuria
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 caspase‐1 inhibitor, WEHD abolished the nicotine‐induced colocalization of NLRP3 with Asc, suggesting the formation of Nlrp3 inflammasomes. Correspondingly, nicotine treatment significantly increased the caspase‐1 activity and IL‐1β production compared to control cells. The prior treatment with WEHD significantly attenuated the nicotine‐induced caspase‐1 activity and IL‐1β 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 nicotine‐induced podocin and nephrin reduction. In addition, prior treatment with ROS inhibitor, NAC significantly attenuated the nicotine‐induced caspase‐1 activity, IL‐1β production and podocin and nephrin reduction in podocytes. Based on these results, it is concluded that nicotine‐induced 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 .