Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China.
J Gastroenterol Hepatol. 2010 Nov;25(11):1777-84. doi: 10.1111/j.1440-1746.2010.06264.x.
Hepatic stellate cells (HSC) are the primary cell type mediating hepatic fibrosis. Although known for its antiviral effects, the inhibitory effects of interferon-beta (IFN-β) on HSC treatment have not yet been established.
Both human and rat activated HSC cell lines were incubated with increasing concentrations of recombinant human IFN-β1a (rhIFN-β1a) for 24, 48 or 72 h. The effects of rhIFN-β1a on α-smooth muscle actin (α-SMA), collagen types I and III, transforming growth factor-β1 (TGF-β1), platelet-derived growth factor-BB (PDGF-BB), and mothers against decapentaplegic homolog (Smad4, Smad7) expression in HSC were examined using Western blotting and immunocytochemistry. Proliferation of HSC was evaluated via bromodeoxyuridine assay.
rhIFN-β1a treatment had a dose-dependent, inhibitory effect on α-SMA and collagen type I protein expression. In addition, rhIFN-β1a decreased the expression of collagen type III, TGF-β1, PDGF-BB and Smad4 protein expression in HSC compared with untreated cells. We also observed increased Smad7 protein expression and decreased proliferation in rhIFN-β1a-treated HSC.
Our data suggest that rhIFN-β1a treatment decreased α-SMA and collagen expression and inhibited the activation of HSC through the inhibition of the TGF-β and PDGF pathways.
肝星状细胞（HSC）是介导肝纤维化的主要细胞类型。干扰素-β（IFN-β）虽然以其抗病毒作用而闻名，但 IFN-β 对 HSC 治疗的抑制作用尚未得到证实。
用不同浓度的重组人干扰素-β1a（rhIFN-β1a）孵育人及大鼠激活的 HSC 细胞系 24、48 或 72 小时。用 Western blot 和免疫细胞化学检测 rhIFN-β1a 对 HSC 中α-平滑肌肌动蛋白（α-SMA）、I 型和 III 型胶原、转化生长因子-β1（TGF-β1）、血小板衍生生长因子-BB（PDGF-BB）和母亲对抗 decapentaplegic 同源物（Smad4、Smad7）表达的影响。通过溴脱氧尿苷测定评估 HSC 的增殖。
rhIFN-β1a 处理对 α-SMA 和 I 型胶原蛋白表达具有剂量依赖性抑制作用。此外，与未处理的细胞相比，rhIFN-β1a 降低了 HSC 中 III 型胶原、TGF-β1、PDGF-BB 和 Smad4 蛋白的表达。我们还观察到 rhIFN-β1a 处理的 HSC 中 Smad7 蛋白表达增加和增殖减少。
我们的数据表明，rhIFN-β1a 处理通过抑制 TGF-β 和 PDGF 通路降低了 α-SMA 和胶原的表达并抑制了 HSC 的激活。
