Novel mode of action of iloprost: in vitro down-regulation of endothelial cell adhesion molecules.
Iloprost is a stable prostacyclin analog commonly employed in the treatment of peripheral vascular disease and also indicated in the treatment of patients affected by systemic sclerosis (SSc) in the presence of severe Raynaud's phenomenon (RP). Several mechanisms of action of the drug other than vasodilation and antiplatelet effect have been demonstrated that may be involved in the exertion of its clinical efficacy. Aim of the present study was to investigate whether iloprost down-regulated lymphocyte adhesion to endothelium through a modulation of adhesion molecule expression on the surface of endothelial cells. In the presence of iloprost, both lymphocyte adhesion and IL-1 stimulated expression of ICAM-1 and ELAM-1 exhibited a significant reduction, while unstimulated adhesion molecule expression was not significantly affected. Our results confirm that iloprost is able to down-regulate lymphocyte adhesion to endothelial cells and indicate that endothelium itself could be target of iloprost administration. Attenuation of the inflammatory response through modulation of cellular interactions could be suggested as a potential mechanism of action of iloprost, when used in the treatment of pathological conditions characterized by endothelial activation.
Della Bella
S
S
Department of Internal Medicine, University of Milan, IRCCS Ospedale Maggiore di Milano, Italy. silvia.dellabella@unimi.it
Molteni
M
M
Mocellin
C
C
Fumagalli
S
S
Bonara
P
P
Scorza
R
R
D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D019040:E-Selectin / Q000032:analysis*; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis*; D007375:Interleukin-1 / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis*
D019040:E-Selectin; D007375:Interleukin-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016285:Iloprost