TY - JOUR
T1 - Microvesicles released from fat-laden cells promote activation of hepatocellular NLRP3 inflammasome
T2 - A pro-inflammatory link between lipotoxicity and non-alcoholic steatohepatitis
AU - Cannito, Stefania
AU - Morello, Elisabetta
AU - Bocca, Claudia
AU - Foglia, Beatrice
AU - Benetti, Elisa
AU - Novo, Erica
AU - Chiazza, Fausto
AU - Rogazzo, Mara
AU - Fantozzi, Roberto
AU - Povero, Davide
AU - Sutti, Salvatore
AU - Bugianesi, Elisabetta
AU - Feldstein, Ariel E.
AU - Albano, Emanuele
AU - Collino, Massimo
AU - Parola, Maurizio
N1 - Publisher Copyright:
© 2017 Cannito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/3
Y1 - 2017/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85014496142&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0172575
DO - 10.1371/journal.pone.0172575
M3 - Article
SN - 1932-6203
VL - 12
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e0172575
ER -