Expression of adhesion molecules by sphingosine 1-phosphate and histamine in endothelial cells

We investigated the effects of sphingosine I-phosphate and histamine on the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, and their signaling pathways in human umbilical vein endothelial cells. Sphingosine 1-phosphate increased the mRNA and protein level of VCAM-1, and the mRNAs of E-selectin and ICAM-1. The effects of sphingosine I-phosphate were inhibited by the pertussis toxin and the respective inhibitors (10 muM 1-[6[[(17beta)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122) for phosphoinositide-specific phospholipase C; 10 muM 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole (SB203580) for p38 mitogen-activated protein kinase (MAPK); I muM 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-metbyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (G66976) for the alpha form of protein kinase C (PKC-alpha)), but not by a PKC-delta inhibitor (I muM rottlerin). Histamine, which alone showed no effect, enhanced the sphingosine I-phosphate-induced expressions via histamine H-1 receptor. The histamine response decreased by U73122 and rottlerin, but not by SB203580 and G66976. The effects of sphingosine I-phosphate with and without histamine were abolished by the higher concentrations of PKC inhibitors and in the PKC-depleted cells. Sphingosine I-phosphate and histamine alone stimulated phosphorylation of p38 MAPK in a phosphoinositide-specific phospholipase C-dependent but not in a PKCs-independent manner. These findings suggest that sphingosine 1-phosphate-induced expression of adhesion molecules was mediated by phosphoinositide-specific phospholipase C and preferentially by PKC-alpha and p38 MAPK, and the histamine response was mediated by phosphoinositide-specific phospholipase C and PKC-delta in human umbilical vein endothelial cells. (C) 2004 Elsevier B.V. All rights reserved.