Effects of dexamethasone on migration of human monocytes in response to oxidized beta-very low density lipoprotein.
OBJECTIVE
We previously showed that dexamethasone inhibited the development of atherosclerosis in cholesterol-fed rabbits. In the present study, we investigated the mechanisms of this inhibition.


METHODS
Monocytes were isolated from the peripheral blood of healthy donors. Cell suspensions were incubated with dexamethasone, 10(-11)-10(-4)M, for 90 minutes at 37 degrees C. Rabbit beta-very low density lipoprotein(beta-VLDL) was obtained from New Zealand White rabbits that had been fed chow containing 1% cholesterol. Oxidative modification of beta-VLDL was performed by auto-oxidation. We measured the migration of monocytes in response to native and oxidized beta-VLDL using a 48-well microchemotaxis chamber.


RESULTS
Oxidized beta-VLDL stimulated the migration of monocytes dose-dependently in the range between 0.5 and 2 nmol/mg protein. Dexamethasone inhibited the chemotaxis of monocytes exposed to oxidized beta-VLDL in a dose-dependent manner more than 10(-9)M.


CONCLUSIONS
Inhibition of the chemotactic response of monocytes exposed to oxidized beta-VLDL may be a mechanism for the anti-atherogenic effect of dexamethasone in cholesterol-fed rabbits.
Yamada
K
K
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Naito
M
M
Hayashi
T
T
Asai
K
K
Yoshimine
N
N
Iguchi
A
A
D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000037:antagonists & inhibitors*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D004036:Diet, Atherogenic; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood; D015227:Lipid Peroxidation; D008079:Lipoproteins, VLDL / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*; D011817:Rabbits; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D002630:Chemotactic Factors; D008079:Lipoproteins, VLDL; D017392:Thiobarbituric Acid Reactive Substances; D003907:Dexamethasone