Cross-linking of intercellular adhesion molecule-1 induces interleukin-8 and RANTES production through the activation of MAP kinases in human vascular endothelial cells.
We investigated whether intercellular adhesion molecule-1 (ICAM-1) transduces outside-in signals for the production of chemokines IL-8 and RANTES in endothelial cells. Cross-linking of ICAM-1 induced IL-8 and RANTES mRNA expressions and increased their protein synthesis and secretions in endothelial cells. Furthermore, ICAM-1 cross-linking activated 44- and 42-kDa mitogen-activated protein (MAP) kinases (ERK1 and ERK2) in endothelial cells, as indicated by the electrophoretic mobility shift of MAP kinases on SDS-polyacrylamide gels. Finally, the specific MEK inhibitor PD98059 inhibited ICAM-1-induced IL-8 and RANTES production in endothelial cells. Taken together, these results indicate that stimulation of ICAM-1 induces IL-8 and RANTES production through the activation of 44- and 42-kDa MAP kinases in endothelial cells, suggesting that ICAM-1-induced chemokine production in endothelial cells would further attract and activate leukocytes to induce intense inflammation.
Department of Internal Medicine II, Chiba University School of Medicine, Chiba, Japan.
H
H
Sano
N
N
Nakagawa
R
R
Chiba
K
K
Kurasawa
Y
Y
Saito
I
I
Iwamoto
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D003432:Cross-Linking Reagents; D004789:Enzyme Activation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D015398:Signal Transduction
D018946:Chemokine CCL5; D003432:Cross-Linking Reagents; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; D017871:Calcium-Calmodulin-Dependent Protein Kinases