Ishizuka T, Kawakami M, Hidaka T, Matsuki Y, Takamizawa M, Suzuki K, Kurita A, Nakamura H
Division of Biomedical Engineering, National Defense Medical College Research Institute, National Defense Medical College, Tokorozawa, Saitama, Japan.
Clin Exp Immunol. 1998 Jun;112(3):464-70. doi: 10.1046/j.1365-2249.1998.00614.x.
A previous study reported that intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells (HUVEC) is augmented by intracellular signal transmission mainly through the protein kinase C (PKC) system stimulated by TXA2 receptors. In the present study, we show that a TXA2 receptor agonist, U46619, augments the expression of not only ICAM-1, but also vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with SQ29,548 (a TXA2 receptor antagonist) or PKC inhibitors greatly diminished the extent of U46619-induced mRNA accumulation and surface expression of the adhesion molecules. An inhibitor of nuclear factor kappaB (NF-kappaB) activation, PDTC, diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-kappaB and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM-1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or ELAM-1 expression of HUVEC stimulated via TXA2 receptors is augmented by induction of NF-kappaB and AP-1 binding activity through the PKC system, and that VCAM-1 expression is augmented by induction of NF-kappaB binding activity.
先前的一项研究报道，人血管内皮细胞（HUVEC）的细胞间黏附分子-1（ICAM-1）表达通过主要由血栓素A2（TXA2）受体刺激的蛋白激酶C（PKC）系统进行的细胞内信号转导而增强。在本研究中，我们发现TXA2受体激动剂U46619不仅能增强HUVEC中ICAM-1的表达，还能在蛋白质和mRNA水平上增强血管细胞黏附分子-1（VCAM-1）或内皮白细胞黏附分子-1（ELAM-1）的表达。用SQ29548（一种TXA2受体拮抗剂）或PKC抑制剂预处理可大大减少U46619诱导的mRNA积累程度和黏附分子的表面表达。核因子κB（NF-κB）激活抑制剂PDTC可减少U46619诱导的VCAM-1 mRNA积累。抑制NF-κB和激活蛋白1（AP-1）结合活性的NAC可在蛋白质和mRNA水平上抑制ICAM-1或ELAM-1的表达。这些发现表明，通过TXA2受体刺激的HUVEC的ICAM-1或ELAM-1表达通过PKC系统诱导NF-κB和AP-1结合活性而增强，并且VCAM-1表达通过诱导NF-κB结合活性而增强。
