Possible Roles of Tumor Necrosis Factor-α and Cytokines in Experimental Hepatocyte Proliferation

Recently, it has been clearly demonstrated that several growth factors, including hepatocyie growth factor (HGF), transforming growth factor-α(TGF-α) , and epidermal growth factor (EGF) , regulate liver cell proliferation in experimental rat models. However, it has been also reported that these growth factors are not always associated with the initial step of liver cell proliferation. Therefore, we focused on the possible roles of cytokines, especially tumor necrosis factor-α(TNF-α) in rat hepatocyte proliferation. The present study, which is introduced in this article, clarifies that hepatocyte proliferation induced in rats by a mitogen, Iead nitrate is suppressed by several TNF-αinhibitors, concluding that TNF-αplays an essential role, that is triggering effect, and regulates necrosis -regeneration processes with hepatocyte proliferation in the course of inflammation. More recently, TNF-αhas been thought to be an initiate or priming factor in the liver cell proliferation or liver regeneration. In this article, we discuss the molecular mechanism of liver cell proliferation, including the roles of TNF-αand other several cytokines as well as the detailed contents of the research article published in 1996 (Y.KUBO,et al. Hepatology 23: 104-1 14)

TNFα

Lead Nituate

Cytokine

Hepatocyte proliferation