@article{ref1,
title="Heatstroke induces liver injury via IL-1β and HMGB1-induced pyroptosis",
journal="Journal of hepatology",
year="2015",
author="Geng, Yan and Ma, Qiang and Liu, Ya-Nan and Peng, Na and Yuan, Fang-Fang and Li, Xing-Gui and Li, Ming and Wu, Ying-Song and Li, Bing-Ling and Song, Wei-Bing and Zhu, Wei and Xu, Wei-Wen and Fan, Jie and Su, Lei",
volume="63",
number="3",
pages="622-633",
abstract="BACKGROUND & AIMS: Liver injury is a common complication of heat stroke (HS), and often constitutes a direct cause for patient death. The cellular and molecular mechanism underlying HS-induced liver injury remains unclear. Recent evidence indicates that inflammasome plays an important role in mediating sterile inflammation triggered by tissue damage. Using a rat HS model, we identified a novel mechanism by which inflammasome-dependent interleukin-1β (IL-1β) activation and hepatocyte pyroptosis mediate HS-induced liver injury. <br><br>METHODS: To induce HS, rats were subjected to heat exposure. Inhibition of inflammasomes was achieved by RNA silencing and pharmacologic inhibitor prior to heat exposure. Inflammasome assembly, caspase-1 activation, histological changes, as well as serum levels of liver enzymes were measured. <br><br>RESULTS: We demonstrated that the onset of HS activated inflammasome in the liver as evidenced by increased capase-1 activity and the association of inflammasome components NOD-like receptor family pyrin domain containing 3 (Nlrp3) and apoptosis speck-like protein containing a caspase-recruitment domain (ASC); and the activated inflammasome, in turn, induced IL-1β activation and hepatocyte pyroptosis, and subsequent augmented liver injury. HS induced hepatocyte inflammasome activation seems to be high-mobility group box 1 (HMGB1) dependent. Inhibition of Nlrp3, caspase-1, or HMGB1 prevented HS-induced liver inflammation and ameliorated liver injury. <br><br>CONCLUSION: These findings demonstrate an important role of HMGB1 in mediating inflammasome activation in the development of liver injury following HS, and suggest that targeting inflammasome may represent a novel therapeutic strategy to limit cell death and prevent liver failure after HS.<p /> <p>Language: en</p>",
language="en",
issn="0168-8278",
doi="10.1016/j.jhep.2015.04.010",
url="http://dx.doi.org/10.1016/j.jhep.2015.04.010"
}