Action of cyclic amp on the expression and release of adhesion
molecules in human endothelial cells.
Morandini1, R., G. Ghanem, A. Portier-Lemari[acute]e, B. Robaye, A.
Renaud, J. M. Boeynaems.
Laboratory of Oncology and Experimental Surgery, Jules Bordet
Institute, Universit[acute]e Libre de Bruxelles, 1000 Brussels,
Belgium, Laboratoires Jacques Logeais, F-78190 Trappes France,
Institute of Interdisciplinary Research, School of Medicine,
Universit[acute]e Libre de Bruxelles, 1070 Brussels Belgium
APStracts 2:0368H, 1995.
The expression of E-selectin induced by tumor necrosis factor (TNF) on
the surface of human umbilical vein endothelial cells (HUVEC) was
partially inhibited by an increase in the level of cyclic adenosine
3',5'-monophosphate (cAMP), produced by forskolin or cholera toxin
combined with the type IV phosphodiesterase inhibitor rolipram, and
by the protein kinase A agonist Sp-cAMPS. The same agents had no
significant effect on the constitutive and TNF-stimulated expression
of intercellular adhesion molecule-1 (ICAM-1), whereas the effect on
vascular cell adhesion molecule-1 (VCAM-1) expression was variable
depending on cell culture conditions. The stimulatory effects of
phorbol 12-myristate,13-acetate (PMA) and bacterial
lipopolysaccharide (LPS) on E-selectin expression were also down
-regulated by the forskolin/rolipram combination and by Sp-cAMPS.
Inhibition of the surface expression of E-selectin was associated
with a decrease of the total amount of the protein in the cell lysate
and a reduced mRNA level, with no significant effect on mRNA
stability. In anesthetized rats, the terbutaline/rolipram combination
reduced the rolling of leukocytes induced by LPS in the mesenteric
microcirculation. In addition to their partial inhibitory effect on
the TNF-induced surface expression of E-selectin on HUVEC, the
forskolin/rolipram combination and Sp-cAMPS strongly inhibited the
release of soluble E-selectin from these cells; the release of
soluble ICAM-1 and VCAM-1 was unaffected by these agents.
Isoproterenol reduced the release of soluble E-selectin, whereas it
had no significant effect on the cell surface expression of the
protein. This study underscores the potential antiinflammatory effect
of a rise in the endothelial cAMP level.
Received 13 February 1995; accepted in final form 14 August 1995.
APS Manuscript Number H128-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.