Induction of the heat shock response in vivo inhibits NF-kappaB activity and protects murine liver from endotoxemia-induced injury.
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-kappaB activation and proinflammatory cytokine expression. Prior induction of HSR significantly attenuated endotoxemia-induced histological changes, inhibited hepatic NF-kappaB activation and IkappaBalpha degradation and decreased mortality. Expression of mRNA coding for TNF-alpha and IL-6 in liver was significantly lower in arsenite-pretreated animals. We conclude that attenuation of endotoxin-induced hepatic NF-kappaB activation and subsequent proinflammatory cytokine production may be one of the mechanisms of the beneficial effect of the heat shock response.
Chen
Dechang
D
Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing.
Pan
Jiaqi
J
Du
Bin
B
Sun
Dongxu
D
D000818:Animals; D018053:Arsenites; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000378:metabolism / Q000517:prevention & control*; D004927:Escherichia coli Infections / Q000378:metabolism / Q000517:prevention & control*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018869:Heat-Shock Response; D020672:I-kappa B Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017670:Sodium Compounds; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D018053:Arsenites; D018840:HSP70 Heat-Shock Proteins; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D017670:Sodium Compounds; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; C017947:sodium arsenite