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IL-17 promotes expression of fibrosis-related factors in hepatic stellate cells
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摘要:
目的研究白细胞介素（IL）17在肝纤维化中的作用及机制。方法腹腔注射CCl4建立小鼠肝纤维化模型,PCR检测肝组织IL-17 mRNA表达变化。大鼠肝星状细胞系（HSC-T6细胞）予以IL-17处理后,PCR检测肌动蛋白α（α-SMA）、胶原蛋白Ⅰ、胶原蛋白Ⅲ、纤维连接蛋白mRNA的表达变化,采用t检验进行比较。免疫组织化学检测肝纤维化患者肝组织中IL-17表达量变化及与α-SMA的关系。结果 CCl4诱导肝纤维化模型小鼠肝组织中IL-17表达明显增加。IL-17促进HSC-T6细胞α-SMA、胶原蛋白Ⅰ、胶原蛋白Ⅲ、纤维连接蛋白mRNA的合成。免疫组织化学结果显示,在肝纤维化患者肝组织中IL-17表达明显增加,并随着纤维化程度加重而逐渐增加,与肝组织表达α-SMA水平呈正相关（r=0.78,P<0.05）。结论 IL-17可促进HSCα-SMA、胶原蛋白Ⅰ、胶原蛋白Ⅲ、纤维连接蛋白mRNA的合成,从而促进肝纤维化的发生发展。
Abstract:Objective To determine whether the observed increased expression of the proinflammatory cytokine interleukin (IL) -17 in fibrotic liver tissues functions to promote fibrosis by mediating the activation of heptatic stellate cells (HSCs) and modulating their expression of fibrosis-related factors, such as alpha-smooth muscle actin (α-SMA) , collagen I, collagen III, and fibronectin.Methods A murine model system of liver fibrosis was established by injecting male C57BL/6J mice (6-8 weeks old) with CCl4 (1.5 μl/g of 1∶6 dilution in olive oil) twice weekly for eight weeks;control mice were similarly injected with olive oil alone.Human liver tissue samples were collected from 32 patients with liver fibrosis (including 19 cases of chronic hepatitis B, three cases of autoimmune hepatitis, six cases of alcoholic liver disease, and four cases of primary biliary cirrhosis) and three healthy controls.The rat HSC-T6 cell line was cultured under standard conditions (controls) or treated with 100 nM of IL-17 for 6 h.Differential expression of IL-17, α-SMA, collagen I, collagen III, and fibronectin mRNA and protein was detected by the real-time fluorescent quantitative PCR or immunohistochemical staining, respectively.Significance of intergroup diffrences was assessed by Student's t-test, and correlation of differences with fibrosis was assessed by calculating the linear correlation coefficient.Results The fibrotic liver tissues from both the mouse model and human patients showed significantly higher IL-17 expression than the non-fibrotic control tissues (mouse mRNA: t=4.84, P<0.01;human protein: t=2.82, P<0.01) .IL-17 treatment of HSC-T6 cells led to significantly increased mRNA expression of α-SMA, collagen I, collagen III, and fibronectin (all P<0.05) .In the human liver tissues, IL-17 protein expression was found to be positively correlated with increased α-SMA protein expression (r=0.78) .Conclusion Enhanced IL-17 in fibrotic liver tissues may act to promote expression of α-SMA, collagen I, collagen III, and fibronectin in HSCs, thereby contributing to the development of liver fibrosis.
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Key words:
- liver cirrhosis /
- interleukin-17 /
- adipocytes
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