Hepatocyte growth factor/scatter factor suppresses TNF-alpha-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.
Makondo
Kennedy
K
Laboratory of Biochemistry, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18-Jou, Nishi 9-choume, 060-0818, Sapporo, Japan
Kimura
Kazuhiro
K
Kitamura
Takanori
T
Yamaji
Daisuke
D
Dong Jung
Bae
B
Shibata
Haruki
H
Saito
Masayuki
M
D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019040:E-Selectin / Q000096:biosynthesis*; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D018922:HL-60 Cells; D017228:Hepatocyte Growth Factor / Q000494:pharmacology* / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D019040:E-Selectin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D017228:Hepatocyte Growth Factor; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III