Glucocorticoid inhibits oxidized LDL-induced macrophage growth by suppressing the expression of granulocyte macrophage colony-stimulating factor

Glucocorticoid, an anti-inflammatory agent, inhibits the development of ath erosclerosis in various experimental animal models. This is partially expla ined by its ability to inhibit smooth muscle cell migration and proliferati on in the intima and to reduce chemotaxis of circulating monocytes and leuk ocytes into the subendothelial spaces. We have recently demonstrated that o xidized LDL (Ox-LDL) has a mitogenic activity for macrophages in vitro in w hich Ox-LDL-induced granulocyte/macrophage colony-stimulating factor (GM-CS F) production plays an important role. Proliferation of cellular components is one of the characteristic events in the development and progression of atherosclerotic lesions. In the present study, we investigated the effects of glucocorticoids on Ox-LDL-induced macrophage growth. Dexamethasone, pred nisolone, and cortisol inhibited Ox-LDL-induced thymidine incorporation int o macrophages by 85%, 70%, and 50%, respectively. Ox-LDL induced a signific ant production of GM-CSF by macrophages, which was effectively inhibited by dexamethasone, prednisolone, and cortisol by 80%, 65%, and 50%, respective ly. Dexamethasone-mediated inhibition of Ox-LDL-induced GM-CSF mRNA express ion and macrophage growth was significantly abrogated by RU-486, a glucocor ticoid receptor antagonist. Our results suggest that the inhibitory effects of glucocorticoids on macrophage growth may be due to the inhibition of Ox -LDL-induced GM-CSF production through transactivation of the glucocorticoi d receptor.