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Induction of the Heat Shock Response In Vivo Inhibits NF-κB Activity and Protects Murine Liver from Endotoxemia-Induced Injury

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Abstract

Liver plays an important role in the pathogenesis of sepsis by releasing various cytokines and producing acute phase proteins. Heat shock preconditioning is reported to be effective in protection of lung and liver from injury in sepsis and in endotoxemia models, but the exact mechanism is still not fully understood. We report here on the effects of the heat shock response (HSR) induced by sodium arsenite on endotoxemia-induced liver injury as well as hepatic NF-κB activation and proinflammatory cytokine expression. Prior induction of HSR significantly attenuated endotoxemia-induced histological changes, inhibited hepatic NF-κB activation and IκBα degradation and decreased mortality. Expression of mRNA coding for TNF-α and IL-6 in liver was significantly lower in arsenite-pretreated animals. We conclude that attenuation of endotoxin-induced hepatic NF-κB activation and subsequent proinflammatory cytokine production may be one of the mechanisms of the beneficial effect of the heat shock response.

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Authors and Affiliations

  1. Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, P. R. China

    Dechang Chen, Jiaqi Pan & Bin Du

  2. Division of Vascular Surgery, Department of Surgery, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229-3900

    Dongxu Sun

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  1. Dechang Chen
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Correspondence to Dongxu Sun.

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Chen, D., Pan, J., Du, B. et al. Induction of the Heat Shock Response In Vivo Inhibits NF-κB Activity and Protects Murine Liver from Endotoxemia-Induced Injury. J Clin Immunol 25, 452–461 (2005). https://doi.org/10.1007/s10875-005-5636-3

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  • DOI: https://doi.org/10.1007/s10875-005-5636-3

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