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Regulation of endothelin and NO on airway wall remodelling

内皮素和NO对气道壁重塑的调节

基本信息

批准号：
10672063
负责人：
KIZAWA Yasuo
金额：
$ 0.38万
依托单位：
Nihon University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672063/
关键词：
remodelling endothelin NO bronchus smooth muscle cultured cells

项目摘要

1. Effects of endothelin-1 (ET-1) and nitric oxide (NO) on the proliferation of cultured guinea pig bronchial smooth muscle were performed by using MTT assay and cell count. ET-1 alone augmented cell proliferation, and also potentiated the effect of epidermal growth factor (EGF) in a concentration-dependent manner. An ETィイD2AィエD2 antagonist, BQ-123, reduced the cell-proliferative effect of ET-1. Furthermore, the cell-proliferative action of ET-1 was partly reduced by a nitric oxide (NO) donor, SIN-1. These results suggest that ET-1 acts not only as a co-mitogen with EGF but also as a mitogen alone, and that its action is mediated through activation of ETィイD2AィエD2 receptors. In addition, the activity may be partly reduced by NO. Therefore, ET-1 may contribute to airway remodelling, a pathophysiological hallmark of asthma.2. Whether ET-1 regulated NO synthesis by the inducible isoform of NO synthase (iNOS) in cultured bronchial smooth muscle cells of guinea pig, using an immunocytochemical technique was in vestigated. In the cultured bronchial cells, constitutive NOS (eNOS) was detected, but iNOS was not found. Exposure to ET-1 for 72 h induced iNOS, and the induction was inhibited by BQ-123. These results suggest that ET-1 induces iNOS via ETィイD2AィエD2 receptor activation in guinea pig bronchial smooth muscle cells. Thus ET-1 may stimulate NO formation not only in epithelial but also smooth muscle cells.

1.采用MTT法和细胞计数法检测内皮素1（ET-1）和一氧化氮（NO）对培养豚鼠支气管平滑肌增殖的影响。 ET-1 单独增强细胞增殖，并且还以浓度依赖性方式增强表皮生长因子 (EGF) 的作用。 ETィイD2AィエD2 拮抗剂 BQ-123 可降低 ET-1 的细胞增殖作用。此外，一氧化氮 (NO) 供体 SIN-1 部分降低了 ET-1 的细胞增殖作用。这些结果表明，ET-1 不仅作为 EGF 的共同有丝分裂原，而且还单独作为有丝分裂原，并且其作用是通过 ETiiD2AiiD2 受体的激活介导的。此外，NO 可能会部分降低活性。因此，ET-1可能有助于气道重塑，这是哮喘的病理生理标志。2．使用免疫细胞化学技术研究了 ET-1 是否通过诱导型 NO 合酶 (iNOS) 在培养的豚鼠支气管平滑肌细胞中调节 NO 合成。在培养的支气管细胞中，检测到组成型NOS（eNOS），但未发现iNOS。暴露于ET-1 72小时诱导iNOS，并且该诱导被BQ-123抑制。这些结果表明，ET-1 通过激活豚鼠支气管平滑肌细胞中的 ETiiD2AiiD2 受体来诱导 iNOS。因此，ET-1不仅可以刺激上皮细胞而且还可以刺激平滑肌细胞中NO的形成。