Interleukin-10 gene therapy reverses thioacetamide-induced liver fibrosis in mice
Interleukin-10 gene therapy reverses thioacetamide-induced liver fibrosis in mice
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DOI：
10.1016/j.bbrc.2005.08.085
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发表时间：
2005-10-14
影响因子：
3.1
通讯作者：
Wang, CH
中科院分区：
文献类型：
--
作者：
Hung, KS;Lee, TH;Wang, CH
肝纤维化代表了慢性肝损伤后的愈合和瘢痕形成过程。白细胞介素-10（IL-10）是一种下调促炎反应并对肝纤维化具有调节作用的细胞因子。本研究旨在探讨IL-10基因治疗是否具有抗小鼠肝纤维化的作用。通过长期硫代乙酰胺给药诱导小鼠肝纤维化。建立肝纤维化模型后，通过电穿孔将人IL-10表达质粒导入。IL-10基因治疗逆转了硫代乙酰胺治疗的肝纤维化并防止了细胞凋亡。RT-PCR显示IL-10基因治疗可降低肝转化生长因子-β 1、肿瘤坏死因子-α、胶原蛋白α 1、细胞粘附分子和金属蛋白酶组织抑制因子mRNA的上调。基因转移后，α-平滑肌肌动蛋白和环氧合酶-2的活化显著减弱。因此，IL-10基因治疗可能是一种有效的肝纤维化治疗药物，具有潜在的临床应用前景。(c)2005年爱思唯尔公司All rights reserved.
Hepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. Interleukin-10 (IL-10) is a cytokine that downregulates the proinflammatory response and has a modulatory effect on hepatic fibrogenesis. The aim of this study was to investigate whether IL-10 gene therapy possesses anti-hepatic fibrogenesis in mice. Liver fibrosis was induced by long-term thioacetamide administration in mice. Human IL-10 expression plasmid was delivered via electroporation after liver fibrosis established. IL-10 gene therapy reversed hepatic fibrosis and prevented cell apoptosis in a thioacetamide-treated liver. RT-PCR revealed IL-10 gene therapy to reduce liver transforming growth factor-beta 1, tumor necrosis factor-alpha, collagen alpha 1, cell adhesion molecule, and tissue inhibitors of metalloproteinase mRNA upregulation. Following gene transfer, the activation of alpha-smooth muscle actin and cyclooxygenase-2 was significantly attenuated. In brief, IL-10 gene therapy might be an effective therapeutic reagent for liver fibrosis with potential future clinical applications. (c) 2005 Elsevier Inc. All rights reserved.