HIV promotes NLRP3 inflammasome complex activation in murine HIV-associated nephropathy

Shabirul Haque, Xiqian Lan, Hongxiu Wen, Rivka Lederman, Amrita Chawla, Mohamed Attia, Ramchandra P. Bongu, Mohammad Husain, Joanna Mikulak, Moin A. Saleem, Waldemar Popik, Ashwani Malhotra, Praveen N. Chander, Pravin C. Singhal

Research output: Contribution to journalArticlepeer-review


Dysregulated growth and loss of podocytes are important features of HIV-associated nephropathy. Recently, HIV was reported to induce a new type of programed cell death, pyroptosis, in T lymphocytes through induction of Nod-like receptor protein 3 (NLRP3) inflammasome complexes. We evaluated the role of HIV in podocyte NLRP3 inflammasome formation both in vivo and in vitro. Renal cortical sections of HIV-transgenic mice (Tg26) displayed increased expression of NLRP3, ASC (a CARD protein), caspase-1, and IL-1β proteins, confirming NLRP3 inflammasome complex formation in podocytes of Tg26 mice. Renal tissues of Tg26 mice also displayed enhanced mRNA levels and protein expressions of inflammasome markers (NLRP3, ASC, and caspase-1, and IL-1β). Serum of Tg26 mice also showed elevated concentrations of IL-1β cytokine compared with FVBN mice. HIV induced pyroptosis in a dose- and time-dependent manner within podocytes, a phenotype of inflammasome activation. Caspase-1 inhibitor not only attenuated podocyte expression of caspase-1 and IL-1β but also provided protection against pyroptosis, suggesting that HIV-induced podocyte injury was mediated by caspase-1 activation. Interestingly, HIV-induced podocyte pyroptosis could be partially inhibited by Tempol (a superoxide dismutase-mimetic agent) and by glyburide (an inhibitor of potassium efflux). These findings suggest that generation of reactive oxygen species and potassium efflux contribute to HIV-induced pyroptosis and NLRP3 inflammasome activation in podocytes.

Original languageEnglish
Pages (from-to)347-358
Number of pages12
JournalAmerican Journal of Pathology
Issue number2
Publication statusPublished - Feb 1 2016

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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