DP-1904, A SPECIFIC INHIBITOR OF THROMBOXANE A(2) SYNTHESIZING ENZYME, SUPPRESSES ICAM-1 EXPRESSION BY STIMULATED VASCULAR ENDOTHELIAL-CELLS

Intercellular adhesion molecule-1 (ICAM-1) is an antigen that is strongly expressed by vascular endothelial cells at sites of local inflammation and participates in the development of inflammation. In the present study, vascular endothelial cells were stimulated by inflammatory cytokines that promote thromboxane A(2) synthesis to observe their effects on the expression and shedding of ICAM-1 on the cell surface. In addition, the suppressive effects of DP-1904 ([+/-]-6-[1-imidazolylmethyl]-5,6,7,s-tetrahydronaphthalene-2- carboxylic acid hydrochloride hemihydrate), a thromboxane A(2) synthesis inhibitor, on ICAM-1 expression were evaluated. ICAM-1 expression on the surface of human umbilical vein endothelial cells was increased significantly by stimulation with interleukin-1 beta, tumor necrosis factor alpha (TNF alpha), thrombin and platelet-activating factor (PAF). DP-1904, an inhibitor of thromboxane A(2) synthesis, significantly suppressed the expression of ICAM-1 on the surface of human vascular endothelial cells that had been stimulated by TNF alpha or PAF. These findings suggest that an enhanced expression of thromboxane A(2) on human vascular endothelial cells is closely related to the expression of ICAM-1 on the surface of these cells.