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Release of granulocyte-mecrophage colony-stimulating factor stimulatd with eosinphil granule proteins and its signal transduction

嗜酸性颗粒蛋白刺激粒细胞-巨噬细胞集落刺激因子的释放及其信号转导

基本信息

批准号：
08670676
负责人：
MOTOJIMA Shinji
金额：
$ 1.47万
依托单位：
Dokkyo Univ.Sch.of Med.
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

In the study of the previous year, we have found that eosinophil-derived basic proteins, namely eosinophil peroxidase (EPO) and major basic protein (MBP), stimulate the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) from bronchial epithelial cells. This year we studied whether tyrosine phosphorylation is involved in the release of GM-CSF.The bronchial epithelial cells were stimulated with EPO (5.9x 10^<-7>M) in the presence or absence of tyrosine phosphorylation inhibitor, herbimycin A (0.2-2.0mug/ml) or genistein (10-100mug/ml), and the release of GM-CSF was evaluated. Both of the tyrosine phosphorylation inhibitors inhibited the release of GM-CSF from the epithelial cells in a concentration-dependent manner. Moreover, the GM-CSF release with IL-1beta and TNF-alpha, very potent stimuli for GM-CSF release, was also completely inhibited with these inhibitors. The proteins which are tyrosine-phosphorylated in terms of molecular weight revealed the same in the stimulation of IL-1beta and EPO by the use of Western blot. Although the GM-CSF release by EPO or MBP does not seem to involve specific receptors, the same signal transduction pathway seems to be utilized as in the case of IL-1beta which has a specific receptor. Further studies are needed to specify the proteins which are tyrosine-phosphorylated and to clarify the signal transduction of EPO and MBP in bronchial epithelial cells in the absence of a specific receptor.

在前一年的研究中，我们发现嗜酸性粒细胞衍生的碱性蛋白，即嗜酸性粒细胞过氧化物酶（EPO）和主要碱性蛋白（MBP），刺激支气管上皮细胞释放粒细胞-巨噬细胞集落刺激因子（GM-CSF）。今年我们研究了酪氨酸磷酸化是否参与GM-CSF的释放。在酪氨酸磷酸化抑制剂herbimycin A （0.2-2.0mug/ml）或染料木素（10-100mug/ml）存在或不存在的情况下，用EPO （5.9 × 10^<-7>M）刺激支气管上皮细胞，评估GM-CSF的释放情况。两种酪氨酸磷酸化抑制剂均以浓度依赖性的方式抑制GM-CSF从上皮细胞的释放。此外，与il -1 β和tnf - α一起释放的GM-CSF也被这些抑制剂完全抑制，而il -1 β和tnf - α是GM-CSF释放的非常有效的刺激。Western blot结果显示，酪氨酸磷酸化的蛋白在il -1 β和EPO的刺激下具有相同的分子量。虽然EPO或MBP释放GM-CSF似乎不涉及特异性受体，但其信号转导途径似乎与具有特异性受体的il -1 β相同。需要进一步的研究来明确酪氨酸磷酸化的蛋白，并澄清EPO和MBP在缺乏特定受体的支气管上皮细胞中的信号转导。