{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T05:18:37Z","timestamp":1790918317077,"version":"4.1.0"},"reference-count":64,"publisher":"Walter de Gruyter GmbH","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The liver plays a central role in the transformation and degradation of endogenous and exogenous chemicals, and in the removal of unwanted cells such as damaged, genetically mutated and virus-infected cells. Because of this function, the liver is susceptible to toxicity caused by the products generated during these natural occurrences. Hepatocyte death is the major feature of liver injury. In response to liver injury, specific intracellular processes are initiated to maintain liver integrity. Inflammatory cytokines including tumor necrosis factor (TNF)\u03b1 and interleukin-6 (IL-6) are key mediators of these processes and activate different cellular response such as proliferation, survival and death. TNF\u03b1 induces specific signaling pathways in hepatocytes that lead to activation of either pro-survival mediators or effectors of cell death. Whereas activation of transcription factor NF-\u03baB promotes survival, c-Jun N-terminal kinases (JNKs) and caspases are strategic effectors of cell death in the TNF\u03b1-mediated signaling pathway. This review summarizes recent advances in the mechanisms of TNF\u03b1-induced hepatotoxicity and suggests that NF-\u03baB plays a protective role against JNK-induced hepatocyte death. Identification of the mechanisms regulating interplay between the NF-\u03baB and JNK pathways is required in the search for novel targets for the treatment of liver disease, including hepatitis and hepatocellular carcinoma.<\/jats:p>","DOI":"10.1515\/bc.2009.111","type":"journal-article","created":{"date-parts":[[2009,7,30]],"date-time":"2009-07-30T15:49:12Z","timestamp":1248968952000},"page":"965-976","source":"Crossref","is-referenced-by-count":143,"title":["Mechanisms of liver disease: cross-talk between the NF-\u03baB and JNK pathways"],"prefix":"10.1515","volume":"390","author":[{"given":"Salvatore","family":"Papa","sequence":"first","affiliation":[{"name":"Department of Immunology, Investigative Science, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Bubici","sequence":"additional","affiliation":[{"name":"Department of Immunology, Investigative Science, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Zazzeroni","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of L'Aquila, I-67100 L'Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Franzoso","sequence":"additional","affiliation":[{"name":"Department of Immunology, Investigative Science, Imperial College London, London W12 0NN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2009,7,30]]},"reference":[{"key":"ref471","first-page":"5","article-title":"Kra hn - 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