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  • Title: [Influence of interferon gamma treatment on expression of TGF-beta1 and its receptors in liver fibrosis of mice with schistosomiasis japonica].
    Author: Zhang BB, Jiao YW, Cai WM, Tao J, Liu RH.
    Journal: Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi; 2004 Dec; 22(6):340-3. PubMed ID: 15830858.
    Abstract:
    OBJECTIVE: To investigate the effect of interferon-gamma (IFN-gamma) on the expression of TGF-beta1 and its two membrane receptors--TGF-beta receptor I (TbetaRI), TGF-beta receptor II (TbetaRII), and observe the expression of TGF-beta1, TbetaRI and TbetaRII during the development of liver fibrosis in BALB/c mice infected by Schistosoma japonicum. METHODS: BALB/c mice, aged 6-8 weeks, were infected with cercariae of S. japonicum. The infected mice were divided randomly into three groups 16 week after infection: model group, praziquantel group and praziquantel combined with IFN-gamma group. Liver specimen were obtained at 8, 12, 16 week and at the end of treatment. Pathological examination, immunohistochemistry and RT-PCR were used to evaluate the pathological change, the expression of TGF-beta1, TbetaRI and TbetaRII and the mRNA level respectively. RESULTS: The expression of TGF-beta1, TbetaRI, and TbetaRII can be detected in infected mice, while the expression around egg granulomas enhanced along with the progress of the disease. With the therapy of IFN-gamma, the reduction of egg granulomas, and of the expression of TGF-beta1, TbetaRI and TbetaRII was observed. From the transcription level, it was found that TGF-beta1 mRNA increased at 12 week and peaked at model group, then decreased to the normal level after treatment with IFN-gamma combined with praziquantel. The level of TbetaRII mRNA reduced at 8 and 16 week and returned to normal at the end of treatment. More interestingly, TbetaRI mRNA remained at the normal level on the whole course both in the development of fibrogenesis and the period of treatment. CONCLUSION: The up regulation of TGF-beta1 and down regulation of TbetaRII mRNA may induce liver fibrogenesis and IFN-gamma might suppress TGF-beta1 to reverse fibrosis. The mechanism of the suppression is mediated by down regulation of expression of its two receptors at protein level but not by influencing the mRNA expression.
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