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2009 Program and Abstracts: Inhibition of IκB Kinase Attenuates Lipopolysaccharide Induced Hepatic Injury
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Inhibition of IκB Kinase Attenuates Lipopolysaccharide Induced Hepatic Injury
Jeremy L. Ward*, Jordan L. Pleitz, Daniel L. Macdougall, David W. Mercer
Department of Surgery, University of Texas Medical School at Houston, Houston, TX

Background: Lipopolysaccharide (LPS) causes hepatic injury that may involve enhanced activity of nuclear factor kappa B (NF-κB) and subsequent changes in expression of oxidative stress proteins such as inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX2). Translocation of inactive NF-κB from the cytosol to the nucleus is prevented by the inhibitory protein IκBα. NF-κB activation usually involves IκB kinase (IKK) phosphorylation of IκBα on two serine residues with resultant dissociation of IκBα from NF-κB. We hypothesized that inhibition of serine phosphorylation of IκBα would diminish hepatic injury and modulate changes in oxidative stress protein caused by LPS.Materials and Methods: Male Sprague-Dawley rats received Bay 11-7085 (10 mg/kg IP), an inhibitor of IκB kinase, or vehicle (DMSO) 1 hour before receiving saline or LPS (20 mg/kg IP). Rats were sacrificed 5 hours after LPS. Serum was collected to measure ALT as an index of hepatic injury. Liver was assessed for iNOS and COX2 (Western blot) protein immunoreactivity (n > 5/group; ANOVA).Results: LPS significantly increased ALT levels and upregulated iNOS and COX2 when compared to controls. Inhibition of IKK with Bay 11-7085 attenuated LPS induced hepatic injury and blunted upregulation of iNOS and COX2 when compared to LPS treated controls. Conclusions: These data indicate that LPS induced hepatic injury is mediated, at least in part, through serine phosphorylation of IκBα which also modulates LPS induced changes in hepatic iNOS and COX2 expression.


Back to Program | 2009 Program and Abstracts | 2009 Posters

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