Iron chelation inhibits NF-kappaB-mediated adhesion molecule expression by inhibiting p22(phox) protein expression and NADPH oxidase activity.
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.


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.
Li
Lixin
L
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA.
Frei
Balz
B
D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D003573:Cytochrome b Group / Q000235:genetics / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D011014:Pneumonia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D015815:Cell Adhesion Molecules; D003573:Cytochrome b Group; D007502:Iron Chelating Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C515614:Cyba protein, mouse; D003676:Deferoxamine; D010100:Oxygen