title: Involvement of anti-inflammatory heme oxygenase-1 in the inhibitory effect of curcumin on the expression of pro-inflammatory inducible nitric oxide synthase in RAW264.7 macrophages.
abstract: Curcumin, at high concentrations (>2 microM), inhibits the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS) through inactivation of nuclear factor (NF)-kappaB 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 microM) can also inhibit NO production and iNOS expression in lipopolysaccharide (LPS)-activated RAW264.7 macrophages only when the cells were pretreated for at least 6h 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-kappaB 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-kappaB activation. Collectively, we provide evidence to support the important role of HO-1 in inhibition of NO production and iNOS expression by curcumin even at low concentrations.
authors.affiliation: Department of Microbiology and Immunology, Wonkwang University School of Medicine, Shin-young Dong, Iksan, Chongbuk 570-749, Republic of Korea.
authors.forename: Ki Mo
authors.initials: KM
authors.lastname: Kim
authors.forename: Hyun-Ock
authors.initials: HO
authors.lastname: Pae
authors.forename: Min
authors.initials: M
authors.lastname: Zhung
authors.forename: Hun-Yong
authors.initials: HY
authors.lastname: Ha
authors.forename: Young Ae
authors.initials: YA
authors.lastname: Ha
authors.forename: Kyu-Yun
authors.initials: KY
authors.lastname: Chai
authors.forename: Yong-Kwan
authors.initials: YK
authors.lastname: Cheong
authors.forename: Jong-Moon
authors.initials: JM
authors.lastname: Kim
authors.forename: Hun-Taeg
authors.initials: HT
authors.lastname: Chung
mesh_terms: D000818:Animals; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D003474:Curcumin