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 and cholesterol-laden J774 macrophages, obtained by pre-incubation with oxidized or acetyla...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
1994-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/S096293519400044X |
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| Summary: | 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 and cholesterol-laden J774 macrophages, obtained by
pre-incubation with oxidized or acetylated low density lipoproteins
(oxLDL, acLDL). Loading with oxLDL caused a small induction of NOS
activity in unstimulated cells, as indicated by nitrite and
citrulline accumulation in the supernatant. However, it suppressed
the iNOS activity resulting from stimulation of the cells with
lipopolysaccharide with or without interferon-γ. AcLDL had no
inhibitory effect, indicating that cholesterol accumulation as such
was not responsible. Since the induction of NOS in macrophages is
inhibited by glucocorticoids, the possibility that a
glucocorticoid-like factor, formed during oxidation of LDL, may
cause the inhibition, was investigated. However, addition of the
glucocorticoid receptor antagonist mifepristone did not prevent the
oxLDL-dependent NOS inhibition, indicating that the glucocorticoid
receptor is not involved in the suppressive effect of oxLDL. |
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| ISSN: | 0962-9351 1466-1861 |