| Literature DB >> 19800575 |
Johannes Haybaeck1, Nicolas Zeller, Monika Julia Wolf, Achim Weber, Ulrich Wagner, Michael Odo Kurrer, Juliane Bremer, Giandomenica Iezzi, Rolf Graf, Pierre-Alain Clavien, Robert Thimme, Hubert Blum, Sergei A Nedospasov, Kurt Zatloukal, Muhammad Ramzan, Sandra Ciesek, Thomas Pietschmann, Patrice N Marche, Michael Karin, Manfred Kopf, Jeffrey L Browning, Adriano Aguzzi, Mathias Heikenwalder.
Abstract
Hepatitis B and C viruses (HBV and HCV) cause chronic hepatitis and hepatocellular carcinoma (HCC) by poorly understood mechanisms. We show that cytokines lymphotoxin (LT) alpha and beta and their receptor (LTbetaR) are upregulated in HBV- or HCV-induced hepatitis and HCC. Liver-specific LTalphabeta expression in mice induces liver inflammation and HCC, causally linking hepatic LT overexpression to hepatitis and HCC. Development of HCC, composed in part of A6(+) oval cells, depends on lymphocytes and IKappa B kinase beta expressed by hepatocytes but is independent of TNFR1. In vivo LTbetaR stimulation implicates hepatocytes as the major LT-responsive liver cells, and LTbetaR inhibition in LTalphabeta-transgenic mice with hepatitis suppresses HCC formation. Thus, sustained LT signaling represents a pathway involved in hepatitis-induced HCC.Entities:
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Year: 2009 PMID： 19800575 PMCID： PMC4422166 DOI： 10.1016/j.ccr.2009.08.021
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743