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

机译:丝裂原活化的蛋白激酶涉及中性粒细胞弹性蛋白酶诱导的人支气管上皮细胞的形态变化。

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摘要

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.
机译:中性粒细胞弹性蛋白酶(NE)促进气道上皮细胞的脱离;但是,NE刺激的支气管上皮细胞(BEC)单层的整体形态变化与胰蛋白酶刺激不同。 Ras / Raf启动的丝裂原活化蛋白激酶(MAPK)也称为细胞外信号调节激酶,其途径调节整联蛋白功能,该功能参与调节细胞的附着和分离以及细胞形态。然而,关于MAPK在NE诱导的BEC整体形态变化中的作用知之甚少。在本研究中,我们检查了MAPK在NE诱导的BEC单层整体形态变化中的作用。为此,我们研究了NE刺激的BEC单层细胞形态和MAPK活化的变化,以及PD 98059作为MAPK激酶-1(MEK-1,MAPK的上游调节剂)对NE诱导的特异性抑制剂的作用。细胞形态和MAPK激活的变化。结果表明,在刺激NE时,BEC分离并出现间隙,并观察到MAPK激活。 PD 98059减弱了NE诱导的细胞形态变化以及MAPK激活。这些结果表明,除了NE在细胞外基质(ECM)上的蛋白水解活性外,NE激活的MAPK途径至少部分参与了NE诱导的整体形态变化和BEC单层的分离。

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