Histamine Enhanced the TNF-α-Induced Expression of E-Selectin and ICAM-1 on Vascular Endothelial Cells

Cell adhesion molecules are expressed on endothelial cells by various proinflammatory cytokines. Tumor necrosis factor-α (TNF-α) 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-α-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 H1receptor antagonists, mepyramine and diphenhydramine. KW-4679 and ketotifen, antiallergic drugs with histamine H1receptor antagonistic activity, potently inhibit the expression of E-selectin and ICAM-1. A histamine H2receptor 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-α through histamine H1receptors.