TitleIron chelation inhibits NF-kappaB-mediated adhesion molecule expression by inhibiting p22(phox) protein expression and NADPH oxidase activity.
Publication TypeJournal Article
Year of Publication2006
AuthorsLi L, Frei B
JournalArterioscler Thromb Vasc Biol
Volume26
Issue12
Pagination2638-43
Date Published2006 Dec
ISSN1524-4636
KeywordsAnimals, Atherosclerosis, Cell Adhesion Molecules, Cytochrome b Group, Deferoxamine, Female, Gene Expression Regulation, Iron Chelating Agents, Lipopolysaccharides, Mice, Mice, Inbred C57BL, NADPH Oxidases, NF-kappa B, Oxidative Stress, Oxygen, Pneumonia, Reactive Oxygen Species, Synovial Membrane
Abstract

OBJECTIVE: Excess iron may increase oxidative stress and play a role in vascular inflammation and atherosclerosis. Here we determined whether the iron chelator, desferrioxamine (DFO), ameliorates oxidative stress and cellular adhesion molecule expression in a murine model of local inflammation.

METHODS AND RESULTS: Dorsal air pouches were created in C57BL/6J mice by subcutaneous injection of air. DFO (100 mg/kg body weight) was injected into the air pouch once a day for two days followed immediately on the second day by lipopolysaccharide (LPS; 2.5 mg/kg body weight). The animals were euthanized 24 hours later for analysis of oxidative stress markers and adhesion molecules in air pouch tissue. LPS treatment enhanced protein levels of p22(phox), a catalytic subunit of NADPH oxidase, and increased NADPH oxidase activity and levels of superoxide radicals and hydrogen peroxide. Furthermore, LPS activated NF-kappaB and increased expression of adhesion molecules. All of these inflammatory responses were strongly suppressed by DFO, but not iron-loaded DFO.

CONCLUSIONS: Our data show that DFO inhibits LPS-induced, NADPH oxidase-mediated oxidative stress and, hence, NF-kappaB activation and adhesion molecule expression in a murine model of local inflammation. Iron chelation may be helpful in treating atherosclerotic vascular diseases by ameliorating oxidative stress and inflammation.

DOI10.1161/01.ATV.0000245820.34238.da
Alternate JournalArterioscler. Thromb. Vasc. Biol.
PubMed ID16973969
Grant ListP01 AT002034 / AT / NCCIH NIH HHS / United States