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
Date Published2006 Dec
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

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.

Alternate JournalArterioscler. Thromb. Vasc. Biol.
PubMed ID16973969
Grant ListP01 AT002034 / AT / NCCIH NIH HHS / United States