Cross-talk between IL-6 and TGF-beta signaling in hepatoma cells.
Interleukin-6 (IL-6) is a multifunctional cytokine that plays important roles in the immune system, hematopoiesis, and acute phase reactions. Transforming growth factor-beta (TGF-beta) also has pleiotropy including the production of acute phase proteins in hepatocytes. To elucidate the cross-talk between IL-6 and TGF-beta signaling pathways in hepatic cells, we investigated the effects of TGF-beta on IL-6-induced signal transducer and activator of transcription-3 (STAT3) activation in a human hepatoma cell line, Hep3B. IL-6-induced activation of STAT3 activity and STAT3-mediated gene expression were augmented by TGF-beta in Hep3B cells. We provide evidence that these activities were due to physical interactions between STAT3 and Sma- and MAD-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.
Department of Immunology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
T
T
Yamamoto
T
T
Matsuda
A
A
Muraguchi
K
K
Miyazono
M
M
Kawabata
D006528:Carcinoma, Hepatocellular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D051900:Smad3 Protein; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; C497790:SMAD3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051900:Smad3 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta