Mitogen-activated protein kinase involves neutrophil elastase-induced morphological changes in human bronchial epithelial cells

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• 作者：Hashimoto ; Shu ; Maruoka ; Shuichiro ; Gon ; Yasuhiro ; Matsumoto ; Ken ; Takeshita ; Ikuko ; Horie ; Takashi
• 关键词：neutrophil elastase ; mitogen-activated protein kinase ; bronchial epithelium
• 刊名：Life Sciences
• 出版年：1999
• 出版时间：March 12, 1999
• 年：1999
• 卷：64
• 期：16
• 页码：1465-1471
• 全文大小：466 K

文摘

Neutrophil elastase (NE) promotes the detachment of airway epithelial cells; however, changes in overall morphology of NE-stimulated bronchial epithelial cell (BEC) monolayer are different from trypsin stimulation. Ras/Raf-initiated-mitogen activated protein kinase (MAPK) also known as extracellular signal-regulated kinase, pathway regulates integrin functions which participate in regulating attachment and detachment of cell and cellular morphology. However, little is known about the role of MAPK in NE-induced changes in overall morphology of BEC. In the present study, we examined the role of MAPK in NE-induced changes in overall morphology of BEC monolayer. To this end, we examined changes in cellular morphology and MAPK activation in NE-stimulated BEC monolayer, and the effect of PD 98059 as the specific inhibitor for MAPK kinase-1 (MEK-1, the upstream regulator of MAPK) on NE-induced changes in cellular morphology and MAPK activation. The results showed that in stimulation of NE, BECs detached and gaps developed, and MAPK activation was observed. PD 98059 attenuated NE-induced changes in cellular morphology as well as MAPK activation. These results indicated that in addition to proteolytic activity of NE on extracellular matrix (ECM), NE-activated MAPK pathway, at least in part, is involved in NE-induced changes in overall morphology and the detachment of BEC monolayer.