FK506 suppresses E-selectin, ICAM-1 and VCAM-1 expression on vascular endothelial cells by inhibiting tumor necrosis factor α secretion from peripheral blood mononuclear cells

FK506 suppresses activation of T cells; however, it down-regulates E-selectin, ICAM-1 and VCAM-1 expression in inflamed tissues. In this study, we investigated the effect of FK506 on expression of those adhesion molecules on human vascular endothelial cells (HMVEC). Culture supernatant from peripheral blood mononuclear cells (PBMC) stimulated with anti-CD3 plus anti-CD2 antibodies effectively induced the expression of E-selectin, ICAM-1 and VCAM-1 on HMVEC, and treatment with FK506 down-regulated their expression. Culture supernatant contained tumor necrosis factor (TNF) α and interleukin (IL)-1β, which effectively induced adhesion molecules, and FK506 suppressed both cytokine secretions. TNFα content in culture supernatant was parallel to the induction of adhesion molecules by the culture supernatant. IL-1β content was not enough to induce those adhesion molecules. Anti-TNFα antibody completely inhibited those expressions. FK506 did not inhibit either TNFα- or IL-1β-induced expression of adhesion molecules, or viability of HMVEC. These results indicate that FK506 suppresses migration of inflammatory cells through the inhibition of TNFα secretion from leukocytes.