کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2107871 | 1083708 | 2009 | 14 صفحه PDF | دانلود رایگان |
SummaryHepatitis B and C viruses (HBV and HCV) cause chronic hepatitis and hepatocellular carcinoma (HCC) by poorly understood mechanisms. We show that cytokines lymphotoxin (LT) α and β and their receptor (LTβR) are upregulated in HBV- or HCV-induced hepatitis and HCC. Liver-specific LTαβ 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 β expressed by hepatocytes but is independent of TNFR1. In vivo LTβR stimulation implicates hepatocytes as the major LT-responsive liver cells, and LTβR inhibition in LTαβ-transgenic mice with hepatitis suppresses HCC formation. Thus, sustained LT signaling represents a pathway involved in hepatitis-induced HCC.
Journal: - Volume 16, Issue 4, 6 October 2009, Pages 295–308