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




Microvesicles released from fat-laden cells promote activation of hepatocellular NLRP3 inflammasome: A pro-inflammatory link between lipotoxicity and non-alcoholic steatohepatitis - Download this document for free, or read online. Document in PDF available to download.

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.



Author: Stefania Cannito , Elisabetta Morello , Claudia Bocca, Beatrice Foglia, Elisa Benetti, Erica Novo, Fausto Chiazza, Mara Rogazzo,

Source: http://plos.srce.hr/



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