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首页> 外文期刊>World Journal of Gastroenterology >Inhibitory effects of interferons on pancreatic stellate cell activation.
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Inhibitory effects of interferons on pancreatic stellate cell activation.

机译：干扰素对胰腺星状细胞活化的抑制作用。

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AIM:To analyze and to compare the effects of interferon (IFN)-alpha, IFN-beta, and IFN-gamma on pancreatic stellate cell (PSC) activation in vitro and to elucidate the molecular basis of IFN action.METHODS:PSCs were isolated from rat's pancreatic tissue, cultured and stimulated with recombinant rat IFNs. Cell proliferation and collagen synthesis were assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine (BrdU) into DNA and ((3)H)-proline into acetic acid-soluble proteins, respectively. Apoptotic cells were determined by FACS analysis (sub-G(1) peak method). Exhibition of the myofibroblastic PSC phenotype was monitored by immunoblot analysis of alpha-smooth muscle actin (alpha- SMA) expression. To assess the activation of signal transducer and activator of transcription (STAT), Western blots using phospho-STAT-specific antibodies were performed. In studies on STAT1 function, expression of the protein was inhibited by siRNA.RESULTS:IFN-beta and IFN-gamma but not IFN-alpha significantly diminished PSC proliferation and collagen synthesis. IFN-gamma was the only IFN that clearly inhibited alpha-SMA expression. Under the experimental conditions used, no enhanced rate of apoptotic cell death was observed in response to any IFN treatment. IFN-beta and IFN-gamma induced a strong increase of STAT1 and STAT3 tyrosine phosphorylation, while the effect of IFN-alpha was much weaker. Inhibition of STAT1 expression with siRNA was associated with a significantly reduced growth-inhibitory effect of IFN-gamma.CONCLUSION:IFN-beta and particularly IFN-gamma display inhibitory effects on PSC activation in vitro and should be tested regarding their in vitro efficiency. Growth inhibition by IFN-gamma action requires STAT1.
机译：目的：分析和比较干扰素（α），干扰素（β）和干扰素（γ）对胰腺星状细胞（PSC）活化的影响，并阐明干扰素作用的分子基础。来自大鼠胰腺组织的细胞，用重组大鼠IFN培养并刺激。细胞增殖和胶原蛋白的合成通过分别测量将5-溴-2'-脱氧尿苷（BrdU）掺入DNA和将（（3）H）-脯氨酸掺入可溶于乙酸的蛋白质来评估。通过FACS分析（sub-G（1）峰值方法）确定凋亡细胞。通过对α-平滑肌肌动蛋白（α-SMA）表达的免疫印迹分析来监测肌纤维母细胞PSC表型的表现。为了评估信号转导子和转录激活子（STAT）的激活，进行了使用磷酸STAT特异性抗体的蛋白质印迹。在STAT1功能的研究中，该蛋白的表达被siRNA抑制。结果：IFN-β和IFN-γ而不是IFN-α显着降低了PSC增殖和胶原合成。 IFN-γ是唯一明显抑制α-SMA表达的IFN。在所使用的实验条件下，未观察到对任何IFN治疗的应答​​，凋亡细胞死亡的速率增加。 IFN-β和IFN-γ引起STAT1和STAT3酪氨酸磷酸化的强烈增加，而IFN-α的作用则弱得多。 siRNA抑制STAT1表达与IFN-γ的生长抑制作用显着降低有关。结论：IFN-β，尤其是IFN-γ在体外对PSC激活具有抑制作用，应对其体外效率进行测试。通过IFN-γ作用抑制生长需要STAT1。

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