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首页> 外文期刊>Journal of endotoxin research >Endotoxin induces leukocyte transmigration and changes in permeability of the airway epithelium via protein-kinase C and extracellular regulated kinase activation.
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Endotoxin induces leukocyte transmigration and changes in permeability of the airway epithelium via protein-kinase C and extracellular regulated kinase activation.

机译：内毒素通过蛋白激酶C和细胞外调节的激酶激活诱导白细胞迁移和气道上皮通透性的变化。

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摘要

Lipopolysaccharide (LPS) endotoxin of Gram-negative bacteria compromises the integrity of the airway epithelial barrier and initiates migration of leukocytes across the epithelium. The goal of the present study was to identify the role of extracellular regulated kinase (ERK1/2) transduction pathways in these processes. The first aim was to determine whether LPS induces ERK1/2 activation and changes in epithelial permeability in epithelial cells alone or only in the presence of immune cells. The second aim was to determine whether the changes in the epithelial permeability were diminished by ERK1/2 blockade. The third aim was to investigate the role of protein kinase C (PKC) activation as an upstream event in activation of ERK1/2. In vitro 20 microg/ml LPS challenge reduced epithelial barrier function, and induced ERK1/2 phosphorylation in primary cultures of bovine tracheal epithelium and in the transformed human airway epithelial cell line, Calu-3. LPS initiated migration of neutrophil-like and monocyte-like transformed HL-60 cell across sheets of Calu-3 cells. The migration rate and the associated changes in the electrical resistance, permeability to albumin, and ERK1/2 phosphorylation were all blocked by calphostin C, the specific blocker of PKC and by PD98059 (2'-amino-3'-methoxyflavone), a selective cell-permeable inhibitor of MAP kinase kinase. In rats, in vivo perfusion of the lumen of an isolated segment of trachea with LPS (0.1 mg/ml) initiated migration of neutrophils and increased the permeability to albumin. Again, these effects were markedly inhibited by PD98059 and calphostin C (by > 50%). We conclude that epithelial ERK1/2 is activated by endotoxin via PKC and is an important pathway in regulation of epithelial permeability.
机译：革兰氏阴性细菌的脂多糖（LPS）内毒素损害气道上皮屏障的完整性，并引发白细胞跨上皮细胞的迁移。本研究的目的是确定细胞外调节激酶（ERK1 / 2）转导途径在这些过程中的作用。第一个目的是确定LPS是仅在上皮细胞中还是仅在存在免疫细胞的情况下，诱导ERK1 / 2激活和上皮通透性变化。第二个目的是确定ERK1 / 2阻滞是否减轻了上皮通透性的变化。第三个目标是研究蛋白激酶C（PKC）激活作为ERK1 / 2激活上游事件的作用。体外20微克/毫升LPS刺激降低了牛气管上皮原代培养物中和转化的人气道上皮细胞系Calu-3中的上皮屏障功能，并诱导ERK1 / 2磷酸化。 LPS启动了中性粒细胞样和单核细胞样转化的HL-60细胞跨Calu-3细胞的迁移。迁移率以及相关的电阻，对白蛋白的渗透性和ERK1 / 2磷酸化的相关变化均被钙磷蛋白C（PKC的特定阻滞剂）和PD98059（2'-氨基-3'-甲氧基黄酮）阻滞了。 MAP激酶激酶的细胞可渗透抑制剂。在大鼠中，LPS（0.1 mg / ml）对气管分离段管腔的体内灌注引发中性粒细胞的迁移并增加了对白蛋白的通透性。同样，PD98059和钙磷蛋白C明显抑制了这些作用（> 50％）。我们得出结论，上皮ERK1 / 2被内毒素通过PKC激活，并且是调节上皮通透性的重要途径。

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