基质金属内肽酶在哮喘炎症发展中的启动作用

We developed two human bronchilal epithelial cell lines which were able to stably express matrix metalloproteinase II(MMP2) and antisense endothelin converting enzyme (ECE-1) RNA respectively with green fluoresce protein as a tracer, by the method of cells transfection using mamanial expression plasmid vector inserted with either MMP2 cDNA or matchable fragment of genomic DNA sequences special for ECE-1 b promotor activation. In addition, it was established that a real-time video micro-tracing system with computer-assistant enables to record and analyze all the information in living cells. Using transient transfection of MMP2/MMP9 expression plasmids in primary epithelial cells, human bronchial epithelial cell(HBEC) line as well as HBECs stably transfected with MMP2 described as above, it mimicked an impairment state in human bronchial epithelial cells under the condition of airway inflammation in asthma. We investigated the effect of over expression of MMP2 in damaged HBECs on subepithelial fibroblasts proliferation, the action of MMP2/MMP9 on producing active endothelin-1(ET-1) in airway constitutive cells , and the interaction between ET-1 and MMPs in asthmatic airway inflammation. It was found that epithelial production of MMP-2 can enhance subepithelial fibroblasts proliferation, a mechanism of which may be associated with that it exerted its effort on processing big ET-1 into active form. Antisense ECE-1 RNA attenuated MMP9 expression in the airway of OVA-sensitized guinea pigs,contributing to a decrease of the recruitment of eosinophiles into the airway. We concluded that the interaction between MMPs and ET-1 produced in airway constitutive cells under the condition of epithelial damage may play an important role in the airway inflammation as well as airway remodeling in the development of asthma.

本课题旨在研究哮喘气道上皮损伤过程中基质金属内肽酶的表达及其对炎细胞迁移、聚集的影响，以及在气道重塑形成中的意义。探讨抗金属内肽酶治疗在控制气道炎症应用中地位。