Abstract:
:Hepatocyte I kappaB kinase beta (IKK beta) inhibits hepatocarcinogenesis by suppressing accumulation of reactive oxygen species (ROS) and liver damage, whereas JNK1 activation promotes ROS accumulation, liver damage, and carcinogenesis. We examined whether hepatocyte p38 alpha, found to inhibit liver carcinogenesis, acts similarly to IKK beta in control of ROS metabolism and cell death. Hepatocyte-specific p38 alpha ablation enhanced ROS accumulation and liver damage, which were prevented upon administration of an antioxidant. In addition to elevated ROS accumulation, hepatocyte death, augmented by loss of either IKK beta or p38 alpha, was associated with release of IL-1 alpha. Inhibition of IL-1 alpha action or ablation of its receptor inhibited carcinogen-induced compensatory proliferation and liver tumorigenesis. IL-1 alpha release by necrotic hepatocytes is therefore an important mediator of liver tumorigenesis.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Sakurai T,He G,Matsuzawa A,Yu GY,Maeda S,Hardiman G,Karin Mdoi
10.1016/j.ccr.2008.06.016subject
Has Abstractpub_date
2008-08-12 00:00:00pages
156-65issue
2eissn
1535-6108issn
1878-3686pii
S1535-6108(08)00226-2journal_volume
14pub_type
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