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目的观察蛙皮素受体亚型-3(bombesin receptor subtype3,BRS-3)激活对人支气管上皮细胞MMP-9/TIMP-1分泌的影响及MMP-9、TIMP-1对人肺成纤维细胞增殖的影响。方法人支气管上皮细胞常规培养,ELISA检测基质金属蛋白酶及其抑制物分泌,MTT检测人肺成纤维细胞增殖。结果(1)臭氧应激使支气管上皮细胞基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶组织抑制剂-1(tissue inhibitor of metalloproteinase-1,TIMP-1)的分泌增加及MMP-9/TIMP-1的比值降低;用特异性人工激动剂P3513激活BRS-3可选择性下调臭氧应激所诱导的MMP-9、TIMP-1的分泌及使MMP-9/TIMP-1的比值增高;激活BRS-3下调支气管上皮细胞分泌MMP-9、TIMP-1的作用可为丝裂原活化蛋白激酶(MAPK)抑制剂PD98059所部分逆转。(2)MMP-9可促进肺成纤维细胞增殖,但TIMP-1对肺成纤维细胞的增殖无显著影响。结论BRS-3激活下调臭氧应激所诱导的支气管上皮细胞MMP-9及TIMP-1分泌,从而改变MMP-9/TIMP-1比值,其机制与丝裂原活化蛋白激酶途径有关;另MMP-9可促进人肺成纤维细胞增殖。上述结果提示BRS-3参与了气道重构,可能在哮喘等气道高反应性疾病中起保护作用。
Objective To investigate the effects of bombesin receptor subtype 3 (BRS-3) activation on the secretion of MMP-9 / TIMP-1 in human bronchial epithelial cells and the effects of MMP-9 and TIMP-1 on the proliferation of human lung fibroblasts Effects of proliferation. Methods Human bronchial epithelial cells were cultured routinely, the secretion of matrix metalloproteinase and its inhibitor was detected by ELISA and the proliferation of human lung fibroblasts was detected by MTT assay. Results (1) Ozone stress increased the secretion of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in bronchial epithelial cells And the ratio of MMP-9 / TIMP-1 decreased. Activation of BRS-3 by a specific artificial agonist P3513 selectively down-regulated the secretion of MMP-9 and TIMP-1 induced by ozone stress, 1 ratio increased; BRS-3 downregulation of bronchial epithelial cells secretion of MMP-9, TIMP-1 role of mitogen-activated protein kinase (MAPK) inhibitor PD98059 part of the reversal. (2) MMP-9 can promote the proliferation of lung fibroblasts, but TIMP-1 has no significant effect on the proliferation of lung fibroblasts. Conclusions BRS-3 activation can down-regulate the secretion of MMP-9 and TIMP-1 in bronchial epithelial cells induced by ozone stress, and thus change the ratio of MMP-9 / TIMP-1, which is related to the mitogen-activated protein kinase pathway. 9 can promote human lung fibroblast proliferation. These results suggest that BRS-3 is involved in airway remodeling and may play a protective role in airway hyperresponsiveness diseases such as asthma.