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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2638.)
© 2006 American Heart Association, Inc.

Vascular Biology

Iron Chelation Inhibits NF-B–Mediated Adhesion Molecule Expression by Inhibiting p22^phox Protein Expression and NADPH Oxidase Activity

Lixin Li; Balz Frei

From the Linus Pauling Institute, Oregon State University, Corvallis.

Correspondence to Balz Frei, PhD, Director and Endowed Chair, Linus Pauling Institute, Oregon State University, 571 Weniger Hall, Corvallis, OR 97331-6512. E-mail balz.frei{at}oregonstate.edu

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-B 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-B 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.

This study shows that the iron chelator, desferrioxamine (DFO), but not iron-loaded DFO, inhibits NF-B activation and cellular adhesion molecule expression in a murine model of local inflammation by inhibiting p22^phox protein expression, NADPH oxidase activity, and oxidant production. Therefore, chelation of excess iron may help attenuate inflammation and atherosclerosis.

Key Words: adhesion molecules • desferrioxamine • LPS • NADPH oxidase

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