OXIDIZED LIPOPROTEINS SUPPRESS NITRIC-OXIDE SYNTHASE IN MACROPHAGES -STUDY OF GLUCOCORTICOID RECEPTOR INVOLVEMENT

ACTIVATED cholesterol-laden macrophages in atherosclerotic lesions are believed to influence the progression of this disease. The induction of nitric oxide synthase (iNOS) activity was investigated in control a nd cholesterol-laden J774 macrophages, obtained by pre-incubation with oxidized or acetylated low density lipoproteins (oxLDL, acLDL). Loadi ng with oxLDL caused a small induction of NOS activity in unstimulated cells, as indicated by nitrite and citrulline accumulation in the sup ernatant. However, it suppressed the iNOS activity resulting from stim ulation of the cells with lipopolysaccharide with or without interfero n-gamma. AcLDL had no inhibitory effect, indicating that cholesterol a ccumulation as such was not responsible. Since the induction of NOS in macrophages is inhibited by glucocorticoids, the possibility that a g lucocorticoid-like factor, formed during oxidation of LDL, may cause t he inhibition, was investigated. However, addition of the glucocortico id receptor antagonist mifepristone did not prevent the oxLDL-dependen t NOS inhibition, indicating that the glucocorticoid receptor is not i nvolved in the suppressive effect of oxLDL.