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

目的：探讨转化生长因子-β-1(转化生长因子-β-1)对人肝内胆管癌细胞的生物学作用。方法：通过检测转化生长因子-β-1对人肝内胆管癌细胞株(HuCCT1、MEC和HU-28)生长的影响以及对细胞内白介素6(IL-6)表达的影响，探讨转化生长因子-β-1对肝内胆管癌细胞生长的影响。对HuCCT1的研究表明，转化生长因子-β-1可刺激转化生长因子-β-1的表达，中和抗转化生长因子-β-1抗体可降低转化生长因子-β-1mRNA的表达。这些结果表明，转化生长因子-β-1以自分泌方式刺激转化生长因子-β-1的产生和功能。此外，在三种细胞系中均可观察到IL-6的分泌，并且对中和抗转化生长因子-β-1抗体有抑制作用。使用HuCCT1的实验表明，转化生长因子-β1诱导的IL-6在蛋白质和基因水平上的表达加速。TH…更多的ESE发现表明转化生长因子-β1和IL-6之间存在功能上的相互作用。在IL-6存在的情况下，这三种细胞系均有增殖。相反，转化生长因子-β-1对细胞表面特异性白介素6受体(IL-6Rα)和信号转导与转录激活子-3(STAT3)的干扰作用不明显。结论：ICC细胞产生转化生长因子-β-1，并以自分泌方式发挥其诱导的生长效应。背景与目的：转化生长因子受体II是转化生长因子β-β信号转导通路的关键分子，参与或参与多种人类疾病的发病机制，因此被认为是治疗和分析转化生长因子-β系统紊乱相关病理生理机制的重要靶点。在肝脏中，转化生长因子-β在肝细胞的凋亡、生长抑制和纤维化的进展中起着重要的作用。迫切需要引入涉及转化生长因子-β系统的技术，例如RNA干扰，它在体内治疗和分析活动方面具有很高的潜力。方法：我们研究了针对转化生长因子-βRII的短发夹状RNA在人和小鼠细胞株和小鼠肝损伤模型中的作用。结果：通过β介导的靶基因沉默和抑制下游信号转导，我们证明了针对转化生长因子RNA干扰RII基因的短发夹状RNA在小鼠和人细胞系中以及急性损伤后肝细胞的生理和形态变化中得以幸免。此外，针对转化生长因子-βRII的短发夹状RNA保护小鼠免受危及生命的急性肝功能衰竭的影响。结论：我们的研究提示转化生长因子-βRII工具可能用于转化生长因子-β信号转导和人类疾病的基因特异性治疗。较少

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