|Title||Iron chelation inhibits NF-kappaB-mediated adhesion molecule expression by inhibiting p22(phox) protein expression and NADPH oxidase activity.|
|Publication Type||Journal Article|
|Year of Publication||2006|
|Authors||Li L, Frei B|
|Journal||Arterioscler Thromb Vasc Biol|
|Date Published||2006 Dec|
|Keywords||Animals, 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 Journal||Arterioscler. Thromb. Vasc. Biol.|
|Grant List||P01 AT002034 / AT / NCCIH NIH HHS / United States|