ICAM-1 signal transduction in cells stimulated with neutrophil elastase
ICAM-1 signal transduction in cells stimulated with neutrophil elastase
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DOI：
10.1007/s10620-006-9178-1
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发表时间：
2006-11-01
影响因子：
3.1
通讯作者：
Ogawa, Michio
中科院分区：
文献类型：
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作者：
Ishihara, Kohjiroh;Yamaguchi, Yasuo;Ogawa, Michio
中性粒细胞弹性蛋白酶可增强内皮细胞细胞间粘附分子-1 （ICAM-1）的表达，在缺血再灌注损伤中起重要作用。在这里，我们研究了中性粒细胞弹性蛋白酶刺激内皮细胞中ICAM-1表达的信号转导。用中性粒细胞弹性酶抑制剂ONO-5046预处理动物。Na显著降低缺血肝叶再灌注后中性粒细胞或Mac-1（+）停止（CD11b/CD18）细胞的数量。中性粒细胞弹性酶刺激后，ICAM-1在大鼠内皮细胞系（WK-5）中的表达明显上调，但这种反应被中性粒细胞弹性酶抑制剂ONO-5046.Na抑制。中性粒细胞弹性酶诱导的ICAM-1 mRNA表达呈剂量依赖性，α 1蛋白酶抑制剂抑制ICAM-1 mRNA表达。中性粒细胞弹性酶刺激下的ICAM-1表达被二酰基甘油激酶抑制剂和蛋白激酶C抑制剂部分降低，但被磷脂酶C抑制剂、胞质Ca（2+）螯合剂、钙调素拮抗剂和核转录因子κ B抑制剂完全抑制。i -125中性粒细胞弹性酶与WK-5细胞的结合被添加未标记的中性粒细胞弹性酶竞争性地抑制。中性粒细胞弹性酶抑制剂显著降低缺血肝叶再灌注后ICAM-1的表达和Mac-1细胞的积累。中性粒细胞弹性蛋白酶通过激活二酰基甘油激酶、蛋白激酶C、磷脂酶C、Ca2+钙调蛋白和核转录因子κ B，通过细胞内信号转导刺激内皮细胞中ICAM-1的表达。
Neutrophil elastase, which enhances intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells, plays an important role in ischemia/reperfusion injury. Here, we investigated signal transduction of ICAM-1 expression in endothelial cells stimulated by neutrophil elastase. Pretreatment of animals with the neutrophil elastase inhibitor, ONO-5046.Na significantly decreased the number of neutrophils or Mac-1(+) stop (CD11b/CD18) cells in ischemic liver lobes after reperfusion. ICAM-1 expression in the rat endothelial cell line (WK-5) was significantly upregulated after stimulation with neutrophil elastase, but this reaction was inhibited by the neutrophil elastase inhibitor ONO-5046.Na. ICAM-1 mRNA expression, which is induced by neutrophil elastase in a dose-dependent manner, was repressed by the alpha 1-protease inhibitor. ICAM-1 expression, stimulated by neutrophil elastase, was partially reduced by a diacylglycerol kinase inhibitor and protein kinase C inhibitor, but was completely inhibited by a phospholipase C inhibitor, cytosolic Ca(2+)chelator, calmodulin antagonist, and nuclear transcription factor kappa B inhibitor. Binding of I-125-neutrophil elastase to WK-5 cells was competitively inhibited by the addition of unlabeled neutrophil elastase. The neutrophil elastase inhibitor significantly reduces ICAM-1 expression and Mac-1 cell accumulation in ischemic liver lobes after reperfusion. Neutrophil elastase stimulates ICAM-1 expression in endothelial cells by intracellular signal transduction via activation of diacylglycerol kinase, protein kinase C, phospholipase C, Ca2+-calmodulin, and nuclear transcription factor kappa B.