| http://purl.uniprot.org/citations/16935850 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16935850 | http://www.w3.org/2000/01/rdf-schema#comment | "TNF-alpha influences morbidity and mortality during the course of endotoxemia. However, the complex pleiotropic functions of TNF-alpha remain poorly understood. We evaluated how hepatic induction of NF-kappaB and TNF-alpha influence survival and hepatocellular death in a lethal murine model of endotoxic shock. Using dominant-negative viral vectors to inhibit the IKK complex, we demonstrate through this study that the liver is a major source of TNF-alpha during the course of lethal endotoxemia and that IKKbeta (but not IKKalpha) is predominantly responsible for activating NF-kappaB and TNF-alpha in the liver after LPS administration. Using TNF-alpha knockout mice and hepatic-specific inhibition of IKKbeta, we demonstrate that the status of TNF-alpha and NF-kappaB balances necrotic and apoptotic fates of hepatocytes in the setting of endotoxemia. In the presence of TNF-alpha, inhibiting hepatic IKKbeta resulted in increased survival, reduced serum proinflammatory cytokines, and reduced hepatocyte necrosis in response to a lethal dose of endotoxin. In contrast, inhibiting hepatic IKKbeta in TNF-alpha knockout mice resulted in decreased survival and increased caspase 3-mediated hepatocyte apoptosis after endotoxin challenge, despite a reduced proinflammatory cytokine response. In the presence of TNF-alpha, NF-kappaB-dependent hepatocellular necrosis predominated, while in the absence of TNF-alpha, NF-kappaB primarily influenced apoptotic fate of hepatocytes. Changes in JNK phosphorylation after LPS challenge were also dynamically affected by both IKKbeta and TNF-alpha; however, this pathway could not solely explain the differential outcomes in hepatocellular fates. In conclusion, our studies demonstrate that induction of NF-kappaB and TNF-alpha balances protective (antiapoptotic) and detrimental (proinflammatory) pathways to determine hepatocellular fates during endotoxemia."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpgi.00043.2006"xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Engelhardt J.F."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Li Q."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Hunninghake G.W."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Monick M.M."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Dajani R."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Sanlioglu S."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Eggleston T."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Davisson R.L."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/author | "Lazartigues E."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/name | "Am J Physiol Gastrointest Liver Physiol"xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/pages | "G242-52"xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/title | "Pleiotropic functions of TNF-alpha determine distinct IKKbeta-dependent hepatocellular fates in response to LPS."xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://purl.uniprot.org/core/volume | "292"xsd:string |
| http://purl.uniprot.org/citations/16935850 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16935850 |
| http://purl.uniprot.org/citations/16935850 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16935850 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J0T4-mappedCitation-16935850 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16935850 |
| http://purl.uniprot.org/uniprot/#_Q0X0E6-mappedCitation-16935850 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16935850 |
| http://purl.uniprot.org/uniprot/#_A0A0R4J210-mappedCitation-16935850 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16935850 |
| http://purl.uniprot.org/uniprot/#_A0A0U5J4W4-mappedCitation-16935850 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16935850 |
| http://purl.uniprot.org/uniprot/#_F6ULQ4-mappedCitation-16935850 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16935850 |