Published online before print September 15, 2005, doi: 10.1161/01.RES.0000186522.89544.4D
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Submitted on March 28, 2005
Revised on July 26, 2005
Accepted on September 8, 2005
Protective Effect of 
-Lipoic Acid in Lipopolysaccharide-Induced Endothelial Fractalkine Expression
Mi Jeong Sung ;
From the Renal Regeneration Laboratory and Departments of Internal Medicine (M.J.S., W.K., S.-O.M., D.H.K., S.L., K.P.K., S.K.P) and Pathology (K.Y.J.), Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju; and Biomedical Research Center and Department of Biological Sciences (S.Y.A., C.-H.C., G.Y.K.), Korea Advanced Institute of Science and Technology, Daejeon, South Korea.
* To whom correspondence should be addressed. E-mail: parksk{at}chonbuk.ac.kr.
Fractalkine is a unique chemokine that functions as a chemoattractant as well as an adhesion molecule on endothelial cells activated by proinflammatory cytokines. Alpha-lipoic acid (LA), a naturally occurring dithiol compound, is an essential cofactor for mitochondrial bioenergetic enzymes. LA improves glycemic control, reduces diabetic polyneuropathies, and mitigates toxicity associated with heavy metal poisoning. The effects of LA on processes associated with sepsis, however, are unknown. We evaluated the antiinflammatory effect of LA on fractalkine expression in a lipopolysaccharide-induced endotoxemia model. Tumor necrosis factor-
(TNF-) and interleukin-1
(IL-1) significantly induced fractalkine mRNA and protein expression in endothelial cells. LA strongly suppressed TNF-- and/or IL-1-induced fractalkine expression in endothelial cells by suppressing the activities of nuclear factor-
B and specificity protein-1. LA also decreased TNF-- or IL-1-stimulated monocyte adhesion to human umbilical vein endothelial cells. As shown by immunohistochemistry, fractalkine protein expression was markedly increased by treatment with lipopolysaccharide in arterial endothelial cells, endocardium, and endothelium of intestinal villi. LA suppressed lipopolysaccharide-induced fractalkine protein expression and infiltration of endothelin 1-positive cells into the heart and intestine in vivo. LA protected against lipopolysaccharide-induced myocardial dysfunction and improved survival in lipopolysaccharide-induced endotoxemia. These results suggest that LA could be an effective agent to reduce fractalkine-mediated inflammatory processes in endotoxemia.
Key words:
-lipoic acid •
fractalkine •
endothelial cells •
inflammation
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