HIV Promotes NLRP3 Inflammasome Complex Activation in Murine HIV-Associated Nephropathy.

HIV Promotes NLRP3 Inflammasome Complex Activation in Murine HIV-Associated Nephropathy.
Am J Pathol. 2015 Dec 10;
Authors: Haque S, Lan X, Wen H, Lederman R, Chawla A, Attia M, Bongu RP, Husain M, Mikulak J, Saleem MA, Popik W, Malhotra A, Chander PN, Singhal PC
Abstract
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 activa...

Source: The American Journal of Pathology - December 10, 2015 Category: Pathology Authors: Haque S, Lan X, Wen H, Lederman R, Chawla A, Attia M, Bongu RP, Husain M, Mikulak J, Saleem MA, Popik W, Malhotra A, Chander PN, Singhal PC Tags: Am J Pathol Source Type: research