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首页> 外文期刊>Journal of Cellular Physiology >Cyclosporine has a direct effect on the differentiation of a mucin-secreting cell line.
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Cyclosporine has a direct effect on the differentiation of a mucin-secreting cell line.

机译:环孢霉素有直接影响mucin-secreting细胞系分化。

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Cyclosporine is a potent immunosuppressant used in the treatment of ulcerative colitis and keratoconjunctivitis sicca. Neither the etiologies of these diseases nor the mechanism by which cyclosporine exerts its therapeutic effect is well understood. Since both diseases are linked by a common decrease in mucin-filled goblet cells, this study tests a hypothesis that cyclosporine acts directly on goblet cells to promote their differentiation and production of secretory mucins. The HT29-18N2 human colon adenocarcinoma cell line, which is capable of forming monolayers of well-differentiated goblet cells, was used as a model system. Cyclosporine induced a dose-dependent increase in intracellular mucin stores. A 2-week exposure to 1 microM cyclosporine resulted in an average increase in mucin volume of 94%. This increase resulted from both a higher percentage of cells with mucin stores and an increased volume of mucin per cell. PSC-833, a nonimmunosuppressive analog of cyclosporine, also increased mucin production. The intracellular accumulation of mucin was not a result of reduced secretion, since the time required for the release of pulse-radiolabeled glycoproteins was similar for both control and cyclosporine-treated monolayers. The effect of cyclosporine was not mediated by the drug's previously documented abilities to decrease cellular proliferation rates, inhibit calmodulin, antagonize prolactin receptor binding, or modulate prostaglandin production. Copyright 2000 Wiley-Liss, Inc.
机译:环孢霉素是一种强有力的免疫抑制剂用于溃疡性结肠炎的治疗角膜结膜炎新铸的卢比。这些疾病的病因和机制环孢霉素对其治疗效果是很好理解的。由一个共同的mucin-filled下降杯状细胞,本研究测试假设环孢霉素直接作用于杯状细胞促进其分化和生产的分泌黏蛋白。腺癌细胞系,有能力成形层的分化良好型的高脚杯细胞,被用来作为一个模型系统。诱导剂量依赖性增加细胞内黏液商店。1 microM环孢霉素导致平均粘蛋白量增加94%。导致细胞的比例更高粘蛋白的商店和体积的增加粘蛋白/细胞。环孢霉素的模拟,也增加粘蛋白生产。粘蛋白没有分泌减少的结果,因为释放所需的时间pulse-radiolabeled糖蛋白是类似的控制和cyclosporine-treated单层膜。环孢霉素的作用不是由药物的先前记录的能力细胞增殖率下降,抑制钙调蛋白,对抗催乳素受体绑定,或者调节前列腺素的生产。版权2000 Wiley-Liss公司。

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