3-Hydroxyanthranilic acid, one of metabolites of tryptophan via indoleamine 2,3-dioxygenase pathway, suppresses inducible nitric oxide synthase expression by enhancing heme oxygenase-1 expression.

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.

authors

Oh GS,Pae HO,Choi BM,Chae SC,Lee HS,Ryu DG,Chung HT

doi

10.1016/j.bbrc.2004.06.061

subject

Has Abstract

pub_date

2004-08-06 00:00:00

pages

1156-62

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006291X04013142

journal_volume

320

pub_type

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