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Am J Physiol Cell Physiol 290: C1092-C1099, 2006. First published November 16, 2005; doi:10.1152/ajpcell.00380.2005
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VASCULAR BIOLOGY

Heme oxygenase-1 mediates the anti-inflammatory actions of 2'-hydroxychalcone in RAW 264.7 murine macrophages

Hadil Abuarqoub, Roberta Foresti, Colin J. Green, and Roberto Motterlini

Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex, United Kingdom

Submitted 28 July 2005 ; accepted in final form 7 November 2005

Chalcones are a group of plant-derived polyphenolic compounds that belong to the flavonoids family, and possess a wide variety of cytoprotective and modulatory functions. Chalcones exert their cytoprotective actions via activation of specific transcriptional factors and upregulation of endogenous defensive pathways, such as phase II enzymes and the stress protein heme oxygenase-1 (HO-1). In this study, we investigated the anti-inflammatory action of 2'-hydroxychalcone (2-HC) in a model of lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages and examined the role of HO-1 in this process. Our results demonstrate that 2-HC potently induces HO-1 expression and markedly reduces LPS-mediated nitrite and TNF-{alpha} production. These effects are accompanied by inhibition of inducible nitric oxide synthase protein expression and abolished by blockade of heme oxygenase activity with either tin protoporphyrin IX or HO-1 small interfering RNA. By using a pharmacological approach and siRNA technology, we also found that phosphatidylinositol 3-kinase is a major cellular mediator in 2-HC-induced HO-1 expression. These findings strongly suggest that 2-HC exerts anti-inflammatory actions via activation of the HO-1 pathway and help to elucidate the mechanisms underlying the potential therapeutic value of chalcones.

lipopolysaccharide; inflammation; nitric oxide


Address for reprint requests and other correspondence: R. Motterlini, Vascular Biology Unit, Dept. of Surgical Research, Northwick Park Institute for Medical Research, Watford Rd., Harrow, Middlesex, HA1 3UJ, UK (e-mail: r.motterlini{at}imperial.ac.uk)






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