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Effects of dexamethasone on migration of human monocytes in response to oxidized beta-very low density lipoprotein
1Department of Geriatrics, Nagoya University School of Medicine, Japan.
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.