Hepatocyte growth factor/scatter factor suppresses TNF-α-induced E-selectin expression in human umbilical vein endothelial cells

Induction of E-selectin on endothelial cell surface initiates leukocyte adhesion and subsequent migration into the subendothelium. Here, we tested the effect of hepatocyte growth factor (HGF) on inflammatory cytokine-induced expression of E-selectin and consequent leukocyte-endothelial cell interaction using human umbilical vein endothelial cells (HUVEC). Prior treatment of HUVEC with HGF significantly attenuated the tumor necrosis factor (TNF)-alpha-induced E-selectin protein, adhesion of HL60 cells to HUVEC and E-selectin mRNA expression in a dose-dependent manner, while HGF itself did not exert any effects. The HGF effects on the mRNA expression were inhibited in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, which also abolished HGF-stimulated eNOS activity. These results suggest HGF plays cardiovascular protective functions mediated, at least in part, through nitric oxide-dependent suppression of inflammatory cytokine-induced E-selectin expression and subsequent tethering of leukocytes to endothelial cells.