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

Life Sci. 1999;64(16):1465-71. doi: 10.1016/s0024-3205(99)00080-6.

Abstract

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.

MeSH terms

  • Bronchi / cytology*
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Adhesion / drug effects
  • Cell Line
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / cytology
  • Flavonoids / pharmacology
  • Humans
  • Leukocyte Elastase / pharmacology*
  • MAP Kinase Kinase 1
  • Mitogen-Activated Protein Kinase Kinases*
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / antagonists & inhibitors

Substances

  • Enzyme Inhibitors
  • Flavonoids
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • Leukocyte Elastase
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one