TY - JOUR
T1 - Protein tyrosine phosphorylation mediates TNF-induced endothelial-neutrophil adhesion in vitro
AU - Kelly, Susan A.
AU - Goldschmidt-Clermont, Pascal J.
AU - Milliken, Emily E.
AU - Arai, Toshiyuki
AU - Smith, Elise H.
AU - Bulkley, Gregory B.
PY - 1998/2
Y1 - 1998/2
N2 - Proinflammatory cytokines initiate the vascular inflammatory response via the upregulation of adhesion molecules on the luminal endothelial surface. We investigated directly the role of protein tyrosine phosphorylation in the upregulation of the endothelial adhesion molecules, intercellular adhesion molecule 1 (ICAM-1) and E-selectin, and the consequent adhesion of neutrophils, after tumor necrosis factor (TNF)-α-stimulation of human aortic endothelial cells in vitro. Time- and dose-dependent TNF-α- stimulated ICAM-1 and E-selectin upregulation and neutrophil adhesion each were suppressed by tyrosine kinase inhibitors, including genistein (200 μM), but not genistin, its isoflavone analog without tyrosine kinase inhibitory activity. Tyrphostin AG 126, a synthetic selective tyrosine kinase inhibitor, also suppressed ICAM-1 and E-selectin upregulation and neutrophil adhesion, each in a dose-dependent manner, whereas tyrphostin AG 1288 had no effect. Tyrosine phosphorylation of two proteins (85 and 145 kDa in the cytoskeleton fraction) found minutes after TNF-α-stimulation was also inhibited by genistein. These findings suggest that, in endothelial cells, TNF-α upregulates ICAM-1 and E-selectin expression and consequent neutrophil adhesion via protein tyrosine phosphorylation.
AB - Proinflammatory cytokines initiate the vascular inflammatory response via the upregulation of adhesion molecules on the luminal endothelial surface. We investigated directly the role of protein tyrosine phosphorylation in the upregulation of the endothelial adhesion molecules, intercellular adhesion molecule 1 (ICAM-1) and E-selectin, and the consequent adhesion of neutrophils, after tumor necrosis factor (TNF)-α-stimulation of human aortic endothelial cells in vitro. Time- and dose-dependent TNF-α- stimulated ICAM-1 and E-selectin upregulation and neutrophil adhesion each were suppressed by tyrosine kinase inhibitors, including genistein (200 μM), but not genistin, its isoflavone analog without tyrosine kinase inhibitory activity. Tyrphostin AG 126, a synthetic selective tyrosine kinase inhibitor, also suppressed ICAM-1 and E-selectin upregulation and neutrophil adhesion, each in a dose-dependent manner, whereas tyrphostin AG 1288 had no effect. Tyrosine phosphorylation of two proteins (85 and 145 kDa in the cytoskeleton fraction) found minutes after TNF-α-stimulation was also inhibited by genistein. These findings suggest that, in endothelial cells, TNF-α upregulates ICAM-1 and E-selectin expression and consequent neutrophil adhesion via protein tyrosine phosphorylation.
KW - E- selectin
KW - Genistein
KW - Human
KW - Intercellular adhesion molecule 1
KW - Polymorphonuclear leukocyte
KW - Tumor necrosis factor
KW - Tyrphostin
UR - http://www.scopus.com/inward/record.url?scp=0031890085&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031890085&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.1998.274.2.h513
DO - 10.1152/ajpheart.1998.274.2.h513
M3 - Article
C2 - 9486255
AN - SCOPUS:0031890085
VL - 274
SP - H513-H519
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
SN - 0363-6143
IS - 2 43-2
ER -