Modulation of ICAM-1 levels on U-937 cells and mouse macrophages by interleukin-1 beta and dexamethasone.
Differentiation of U-937 cells with phorbol ester (10 nM) induced a time-dependent (24 h or 48 h) increase of adhesion molecules and lipocortin 1 expression on the cell surface. Stimulation with interleukin-1 beta for a further 16 h increased the levels of intercellular adhesion molecule-1, and this effect was inhibited by co-incubation with 0.1-1 microM dexamethasone. The effect of the glucocorticoid was not modified by addition of a specific anti-lipocortin 1 monoclonal antibody (mAb 1A, 5 micrograms/ml). This opposite modulatory role of interleukin-1 and dexamethasone on intercellular adhesion molecule-1 expression was also, for the first time, observed in vivo using mouse peritoneal macrophages: a four-fold increase in intercellular adhesion molecule-1 expression was measured after local administration of the cytokine (5 micrograms/kg) and this effect was greatly inhibited (> 70%) by co-injection with 1 microgram dexamethasone. In conclusion, modulation of intercellular adhesion molecule-1 expression by glucocorticoids is an effect independent endogenous lipocortin 1, and it is an in vivo feature of these potent anti-inflammatory drugs.
Perretti
M
M
Department of Biochemical Pharmacology, William Harvey Research Institute, Medical College, St. Bartholomew's Hospital, London, United Kingdom.
Wheller
S K
SK
Harris
J G
JG
Flower
R J
RJ
D000818:Animals; D017305:Annexin A1 / Q000096:biosynthesis / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D013997:Time Factors
D017305:Annexin A1; D000911:Antibodies, Monoclonal; D015214:Antigens, Differentiation, Myelomonocytic; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D005938:Glucocorticoids; D016167:Integrin alphaXbeta2; D007375:Interleukin-1; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone