Abstract:
:Inducible nitric oxide (NO) synthase (iNOS), heme oxygenase (HO)-1, and indoleamine 2,3-dioxygenase (IDO) are simultaneously expressed in murine macrophages stimulated with interferon (IFN)-gamma and lipopolysaccharide (LPS). NO produced by iNOS suppresses IDO expression and also induces HO-1 expression. The antioxidant 3-hydroxyanthranilic acid (HA), one of metabolites of tryptophan via IDO pathway, has been previously reported to suppress iNOS expression. Because HO-1 expression can suppress iNOS expression, we investigated whether HA could suppress iNOS expression by affecting HO-1 expression in murine RAW 264.7 macrophages stimulated with IFN-gamma plus LPS. Treatment with exogenous HA dose-dependently suppressed iNOS expression and coincidently enhanced HO-1 expression. This suppressive effect of HA on iNOS expression was reversed by blocking HO-1 activity, and proven to be due to carbon monoxide (CO) produced by HO-1. In addition, either blocking of iNOS activity or addition of exogenous CO further enhanced IDO expression and activity. These results show for the first time that HA is able to suppress iNOS expression by enhancing HO-1 expression, thereby resulting in further increases in IDO expression and activity.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Oh GS,Pae HO,Choi BM,Chae SC,Lee HS,Ryu DG,Chung HTdoi
10.1016/j.bbrc.2004.06.061subject
Has Abstractpub_date
2004-08-06 00:00:00pages
1156-62issue
4eissn
0006-291Xissn
1090-2104pii
S0006291X04013142journal_volume
320pub_type
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