Application of IL-6 HGF, TGF beta 1 for a bile duct cancer treatment.

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AIM : To elucidate the biological effects of transforming growth factor-β1 (TGF-β1) on intrahepatic cholangiocarcinoma (ICC).METHODS : We investigated the effects of TGF-β1 on human ICC cell lines (HuCCT1, MEC, and HuH-28) by monitoring the influences of TGF-β1 on tumor growth and interleukin-6 (IL-6) expression in ICC cells.RESULTS : All three human ICC cell lines produced TGF-β1 and accelerated growth in the presence of TGF-β1 with no apoptotic effect. Studies on HuCCT1 revealed a TGF-β1-induced stimulation of the expression of TGF-β1, as well as a decrease in TGF-β1 mRNA expression induced by neutralizing anti-TGF-β1 antibody. These results indicate that TGF-β1 stimulates the production and function of TGF-β1 in an autocrine fashion. Further, IL-6 secretion was observed in all three cell lines and exhibited an inhibitory response to neutralizing anti-TGF-β1 antibody. Experiments using HuCCT1 revealed a TGF-β1-induced acceleration of IL-6 expression in the protein and mRNA levels. Th … More ese findings demonstrate a functional interaction between TGF-β1 and IL-6. All three cell lines proliferated in the presence of IL-6. In contrast, TGF-β1 induced no growth effect in HuCCT1 with small interfering RNA against a specific cell surface receptor of IL-6 (IL-6Rα) and signal transducer and activator of transcription-3 (STAT3).CONCLUSION : ICC cells produce TGF-β1 and confer a TGF-β1-induced growth effect in an autocrine fashion. TGF-β1 activates IL-6 production, and the functional interaction between TGF-β1 and IL-6 contributes to ICC cell growth by TGF-β1. Background & Aims : Transforming growth factorβ (TGF-β) receptor II (TGF-βRII), which is essential for TGF-β signaling and is involved in the causation or participates in the pathway of various human disorders, is consequently considered a key target for therapeutics and analysis of the pathophysiology associated with disruption of the TGF-β system. In the liver, TGF-β plays an essential role in hepatocyte apoptosis, growth inhibition, and progression of fibrogenesis. There is a critical need to introduce technology involving the TGF-β system, such as RNA interference (RNAi), which has high potential for in vivo therapeutics and analytical activities. Methods : Here, we investigated the effect of short hairpin RNA targeting TGF-βRII in human and mouse cell lines and liver injury mouse models. Results : We demonstrated that short hairpin RNA targeting TGFβRII genes in mouse and human cell lines, and physiologic and morphologic changes in hepatocytes suffering from acute injury are spared by RNAi-mediated gene silencing of the target gene and by suppressing downstream signal transduction. Furthermore, short hairpin RNA targeting TGF-βRII protected mice from life-threatening acute liver failure. Conclusions : Our study suggests the potential use of TGF-βRII tool for TGF-β signaling and gene-specific therapy in human disorders. Less