Cross-talk between IL-6 and TGF-beta signaling in hepatoma cells

Interleukin-6 (IL-6) is a multifunctional cytokine that plays important rol es in the immune system, hematopoiesis, and acute phase reactions. Transfor ming growth factor-beta (TGF-beta) also has pleiotropy including the produc tion of acute phase proteins in hepatocytes, To elucidate the cross-talk be tween IL-6 and TGF-beta signaling pathways in hepatic cells, we investigate d the effects of TGF-beta on IL-6-induced signal transducer and activator o f transcription-3 (STAT3) activation in a human hepatoma cell line, Hep3B, IL-6-induccd activation of STAT3 activity and STAT3-mediated gene expressio n were augmented by TGF-beta in Hep3B cells, We provide evidence that these activities were due to physical interactions between STAT3 and Sma- and MA D-related protein-3, bridged by p300. These results demonstrate a molecular mechanism of a cross-talk between STAT3 and TGF-beta signaling pathways in hepatocytes, (C) 2001 Federation of European Biochemical Societies. Publis hed by Elsevier Science B.V. All rights reserved.