Mechanisms for regulation of cellular responsiveness to human IFN-β1a

Mechanisms for regulation of cellular responsiveness to human IFN-β1a
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DOI:
10.1089/10799900252952280
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发表时间:
2002-04-01
影响因子:
2.3
通讯作者:
Green, M
Green, M
中科院分区:
医学4区
文献类型:
--
作者:
Dupont, SA;Goelz, S;Green, M

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干扰素(IFN)是一种强大的、多效性的细胞因子,因此,细胞可能具有调节干扰素活性的机制,以应对过量或长期的干扰素暴露。为了研究这个问题,我们在体外将Jurkat T细胞暴露于干扰素-β1a。检测不同剂量和频率的干扰素对受体表达、信号转导途径和生物活性的影响。结果表明,即使是中等剂量的干扰素(60IU/ml),细胞表面干扰素受体亚单位IFNAR-1的表达也显著下降,细胞对进一步的干扰素治疗没有反应。更有趣的是,在最初使用非常低浓度的干扰素(
Interferons (IFNs) are potent, pleiotropic cytokines, and therefore it is likely that the cell has mechanisms to modulate IFN activity in response to excessive or prolonged IFN exposure. To investigate this question, Jurkat T cells were exposed to IFN-beta1a in vitro. The effect of dose and frequency of IFN treatment on receptor expression, the signal transduction pathway, and biologic activity was examined. Results demonstrate that at even modest doses of IFN (60 IU/ml), cell surface expression of the IFN receptor subunit, IFNAR-1, decreased significantly, and the cells were unresponsive to further IFN treatment. More interestingly, after an initial treatment with very low concentrations of IFN (