期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 62, 期 9, 页码 630-636出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2008.01.008
关键词
Curcumin; Inducible nitric oxide synthase; Heme oxygenase-1; Nuclear factor-kappa B
资金
- Wonkwang University
Curcumin, at high concentrations (>2 mu M), inhibits the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS) through inactivation of nuclear factor (NF)-kappa B and, at low concentrations. induces the expression of heme oxygenase (HO)-1 in macrophages. Here, we demonstrated that curcumin at low concentrations (0.5-2 mu M) can also inhibit NO production and iNOS expression in lipopolysaccharide (LPS)-activated RAW264.7 macrophages only when the cells were pretreated for at least 6 h with curcumin. Curcumin induced dose- and time-dependent HO-1 expression, and this was coincident with the inhibitory effects of low concentrations of curcumin on NO production and iNOS expression. Blockage of HO-1 activity or knockdown of HO-1 expression abolished the inhibitory effects of curcumin. Over-expression of HO-1 or exogenous addition of carbon monoxide, a byproduct derived from heme degradation, mimicked the inhibitory action of low concentrations of curcumin. Moreover, LPS-induced NF-kappa B was diminished in macrophages subjected to prolonged treatment with low concentrations of curcumin. Treatment with HO inhibitor abolished the inhibitory effect of curcumin on LPS-induced NF-kappa B activation. Collectively, we provide evidence to support the important role of HO-1 in inhibition of NO production and iNOS expression by curcurnin even at low concentrations. (C) 2008 Elsevier Masson SAS. All rights reserved.
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