Subacute treatment of rats with dexamethasone reduces ICAM-1 levels on circulating monocytes.
We report for the first time that in vivo treatment with dexamethasone (DEX) reduces levels of intercellular adhesion molecule-1 (ICAM-1) expression on rat circulating unstimulated monocytes (-55%) and peritoneal macrophages (-26%). This effect was present following sub-acute (5 days) treatment with a low dose (0.1 mg/kg per day), but not after single administration of a high dose (1 mg/kg, -2 h), of the steroid. Both acute and sub-acute treatment with DEX failed to modify either basal or up-regulated CD11b expression on peripheral blood monocytes and neutrophils, elastase release from neutrophils, and beta-glucuronidase release from cultured macrophages. The lack of alteration of CD11b expression on circulating leukocytes suggests that the effect of DEX on ICAM-1 expression is secondary to gene repression rather than a non-specific blockade of cell differentiation. These data promote the concept that different dose-regimens with glucocorticoids affect distinct molecular targets and indicate that clinically-related protocols of DEX may reveal new mechanism(s) of action.
Tailor
A
A
Department of Biochemical Pharmacology, William Harvey Research Institute, London, United Kingdom.
Das
A M
AM
Getting
S J
SJ
Flower
R J
RJ
Perretti
M
M
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D019272:Leukocyte Elastase / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D005938:Glucocorticoids; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D019272:Leukocyte Elastase