S. Hashimoto et al., Mitogen-activated protein kinase involves neutrophil elastase-induced morphological changes in human bronchial epithelial cells, LIFE SCI, 64(16), 1999, pp. 1465-1471
Neutrophil elastase (NE) promotes the detachment of airway epithelial cells
; however, changes in overall morphology of NE-stimulated bronchial epithel
ial cell (BEC) monolayer are different from trypsin stimulation. Ras/Raf-in
itiated-mitogen activated protein kinase (MAPK) also known as extracellular
signal-regulated kinase, pathway regulates integrin functions which partic
ipate in regulating attachment and detachment of cell and cellular morpholo
gy. However, little is known about the role of MAPK in NE-induced changes i
n overall morphology of BEG. 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-s
timulated BEC monolayer, and the effect of PD 98059 as the specific inhibit
or for MAPK kinase-l (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 activatio
n was observed. PD 98059 attenuated NE-induced changes in cellular morpholo
gy 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 mo
rphology and the detachment of BEC monolayer.