Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration.
Salicylates inhibit I kappa B-alpha phosphorylation, endothelial-leukocyte adhesion molecule expression, and neutrophil transmigration.
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DOI：
10.4049/jimmunol.156.10.3961
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发表时间：
1996-05
影响因子：
4.4
通讯作者：
J. W. Pierce;M. Read;H. Ding;F. Luscinskas;T. Collins
中科院分区：
文献类型：
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作者：
J. W. Pierce;M. Read;H. Ding;F. Luscinskas;T. Collins
白细胞粘附分子在内皮细胞上的表达是由tnf - α和其他炎性细胞因子诱导的。这种内皮-白细胞粘附分子-1、血管细胞粘附分子-1和细胞间粘附分子-1的诱导需要转录因子核因子- κ B （nf - κ B）。最近的研究表明，一些非甾体抗炎药，包括水杨酸钠和阿司匹林，可以抑制nf - κ b依赖基因的激活。我们研究了水杨酸酯对HUVECs粘附分子表达的影响。我们发现水杨酸钠通过阻止抑制剂1 kappa B- α的磷酸化和随后的降解来抑制NF-kappa B （p50/p65和p65/p65）的活化。水杨酸治疗对tnf α诱导的转录因子ATF-2的磷酸化没有影响。水杨酸阻断了tnf - α诱导的粘附分子mRNA水平的升高，并对tnf - α诱导的血管细胞表面粘附分子-1和细胞间粘附分子-1的表达产生剂量依赖性抑制，需要更高剂量才能抑制内皮-白细胞粘附分子-1的表达。非水杨酸类环加氧酶抑制剂吲哚美辛对粘附分子的表面表达无影响，提示其作用不是由于对环加氧酶的抑制。用水杨酸钠处理内皮细胞单层可抑制中性粒细胞的跨内皮迁移，但对流动条件下的中性粒细胞粘附无显著影响。高剂量水杨酸盐在炎症中的临床重要性可能部分是由于它能够阻止诱导粘附分子的表达和白细胞的募集。
The expression of leukocyte adhesion molecules on endothelial cells is induced by TNF-alpha and other inflammatory cytokines. This induction of endothelial-leukocyte adhesion molecule-1, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 requires the transcription factor nuclear factor-kappa B (NF-kappa B). Recent work has suggested that some nonsteroidal anti-inflammatory agents, including sodium salicylate and aspirin, can inhibit NF-kappa B-dependent gene activation. We studied the effects of salicylates on expression of adhesion molecules in HUVECs. We found that sodium salicylate inhibited activation of NF-kappa B (p50/p65 and p65/p65) by preventing phosphorylation and subsequent degradation of the inhibitor 1 kappa B-alpha. Salicylate treatment had no effect on TNF-alpha-induced phosphorylation of the transcription factor ATF-2. Salicylate blocked the TNF-alpha-induced increase in mRNA levels of adhesion molecules and gave a dose-dependent inhibition of TNF-alpha-induced surface expression of vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 with higher doses required to inhibit endothelial-leukocyte adhesion molecule-1 expression. Indomethacin, a nonsalicylate cyclooxygenase inhibitor, had no effect on surface expression of adhesion molecules, suggesting that the effects were not due to inhibition of cyclooxygenase. Treatment of endothelial cell monolayers with sodium salicylate inhibited transendothelial migration of neutrophils but had no significant effect on neutrophil adhesion under flow conditions. The clinical importance of high-dose salicylates in inflammation may be due, in part, to the ability to prevent expression of inducible adhesion molecules and recruitment of leukocytes.