Inhibition of cytokine production and adhesion molecule expression by ibuprofen is without effect on transendothelial migration of monocytes.
The present study focusses on the effects of ibuprofen and its enantiomers on cytokine production by peripheral blood monocytes and endothelial cells as well as on the potential modulation of ADM-expression by human umbilical vein endothelial cells and the concomitant effects on monocyte transendothelial migration as measured by a cell migration assay system. This consists of an endothelial cell monolayer on a solid collagen substrate, i.e. an artificial vessel wall construct. We observed a significant inhibition by 100 microg/ml ibuprofen of VCAM-1 expression by endothelial cells while ELAM-1 and ICAM-1 expression was not influenced. However, we could not see any concomitant inhibitory effects on the spontaneous migration of monocytes after preincubating the endothelial cell monolayer with ibuprofen up to concentrations of 100 microg/ml and activating with suboptimal and optimal concentrations of TNF-alpha. Our monocyte transendothelial migration system reflects very sensitively endothelial cell-activation even by very low TNF-alpha concentrations. (S)- and (R)-ibuprofen were equal in their inhibitory/activating effects on cytokine production, with the exception of stronger IL-8 induction in endothelial cells by (R)-ibuprofen as compared to its chiral analogue.
Institute of Immunology, University of Vienna, Austria.
E J
EJ
Menzel
H
H
Burtscher
G
G
Kolarz
D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D004306:Dose-Response Relationship, Immunologic; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007052:Ibuprofen