Effects of damage on endothelin production in epithelial cells and sub-epithelial fibroblasts / 中国病理生理杂志

ABSTRACT

AIM: To investigate the level of ET-1 produced by cultured human bronchial epithelial cells (HBECs) under injury and the effects of injured HBECs on ET-1 production in sub-epithelial fibroblasts. The interaction between ET-1 and matrix metalloproteinase-9(MMP-9) was detected in HBECs under damage. The purpose of the study is to evaluate the effect of injured HBECs related to ET-1 release on airway remodeling in asthma. METHODS: ET-1 level was detected in supernatants from cultured HBECs 12 h after being treated with either mechanical scraping or LPS stimulation or mechanical scraping plus LPS, as well as from subepithelial fibroblasts cocultured with mechanical damaged HBECs. It was also measured in the supernatant from HBECs transfected with MMP-9 expression plasmid. MMP-9 activity was assessed in supernatants from HBECs stably transfected with pEGFPc1 -antisense-ET-1 converting enzyme(ECE) RNA. RESULTS: It was found that there was an increase in ET-1 level in supernatants from HBECs either treated with mechanical scraping plus LPS or transiently transfected with MMP-9 plasmid, as well as from sub-epithelial fibroblasts cocultured with mechanical scraping HBECs compared with that in controls. Gelatin zymography showed a obviously attenuated gelatinolytic activity of MMP-9 in conditioned media of HBECs expressing antisense ECE RNA after mechanical damage. CONCLUSIONS: Airway epithelial cells under injury are able to overproduce ET-1 as well as initiate ET-1 release from sub-epithelial fibroblasts, MMP-9 produced by injured bronchial epithelial cells may also increase ET-1 processing leading to ET-1 production further. The interaction between ET-1 and MMP-9, both of which enhanced in damaged HBECs, may play an important role in airway inflammation related to airway remodeling in asthma.