Miki I, Kusano A, Ohta S, Hanai N, Otoshi M, Masaki S, Sato S, Ohmori K
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Cell Immunol. 1996 Aug 1;171(2):285-8. doi: 10.1006/cimm.1996.0205.
Cell adhesion molecules are expressed on endothelial cells by various proinflammatory cytokines. Tumor necrosis factor-alpha (TNF-alpha) induces the expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVEC). Although histamine is a potent vasoactive mediator, it does not induce the expression of E-selectin and ICAM-1. In this report, we show that histamine concentration-dependently enhances the TNF-alpha-induced expression of E-selectin and ICAM-1 on HUVEC. The histamine-enhanced expression of E-selectin and ICAM-1 was inhibited by the histamine H1 receptor antagonists, mepyramine and diphenhydramine. KW-4679 and ketotifen, antiallergic drugs with histamine H1 receptor antagonistic activity, potently inhibit the expression of E-selectin and ICAM-1. A histamine H2 receptor antagonist, ranitidine, did not affect the histamine-induced expression of cell adhesion molecules. These data indicate that histamine induces the expression of E-selectin and ICAM-1 synergistically with TNF-alpha through histamine H1 receptors.
细胞黏附分子由多种促炎细胞因子在内皮细胞上表达。肿瘤坏死因子-α（TNF-α）可诱导人脐静脉内皮细胞（HUVEC）表达E-选择素和细胞间黏附分子-1（ICAM-1）。虽然组胺是一种强效血管活性介质，但它不会诱导E-选择素和ICAM-1的表达。在本报告中，我们表明组胺以浓度依赖性方式增强TNF-α诱导的HUVEC上E-选择素和ICAM-1的表达。组胺增强的E-选择素和ICAM-1表达受到组胺H1受体拮抗剂美吡拉敏和苯海拉明的抑制。具有组胺H1受体拮抗活性的抗过敏药物KW-4679和酮替芬可有效抑制E-选择素和ICAM-1的表达。组胺H2受体拮抗剂雷尼替丁不影响组胺诱导的细胞黏附分子表达。这些数据表明，组胺通过组胺H1受体与TNF-α协同诱导E-选择素和ICAM-1的表达。
