Microvesicles released from fat-laden cells promote activation of hepatocellular NLRP3 inflammasome: A pro-inflammatory link between lipotoxicity and non-alcoholic steatohepatitis

Stefania Cannito, Elisabetta Morello, Claudia Bocca, Beatrice Foglia, Elisa Benetti, Erica Novo, Fausto Chiazza, Mara Rogazzo, Roberto Fantozzi, Davide Povero, Salvatore Sutti, Elisabetta Bugianesi, Ariel E. Feldstein, Emanuele Albano, Massimo Collino, Maurizio Parola

Risultato della ricerca: Contributo su rivistaArticolo in rivistapeer review

Abstract

Non-Alcoholic Fatty Liver Disease (NAFLD) is a major form of chronic liver disease in the general population in relation to its high prevalence among overweight/obese individuals and patients with diabetes type II or metabolic syndrome. NAFLD can progress to steatohepatitis (NASH), fibrosis and cirrhosis and end-stage of liver disease but mechanisms involved are still incompletely characterized. Within the mechanisms proposed to mediate the progression of NAFLD, lipotoxicity is believed to play a major role. In the present study we provide data suggesting that microvesicles (MVs) released by fat-laden cells undergoing lipotoxicity can activate NLRP3 inflammasome following internalization by either cells of hepatocellular origin or macrophages. Inflammasome activation involves NF-kB-mediated up-regulation of NLRP3, pro-caspase-1 and pro-Interleukin-1, then inflammasome complex formation and Caspase-1 activation leading finally to an increased release of IL-1β. Since the release of MVs from lipotoxic cells and the activation of NLRP3 inflammasome have been reported to occur in vivo in either clinical or experimental NASH, these data suggest a novel rational link between lipotoxicity and increased inflammatory response.

Lingua originaleInglese
Numero di articoloe0172575
RivistaPLoS ONE
Volume12
Numero di pubblicazione3
DOI
Stato di pubblicazionePubblicato - mar 2017

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