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Journal of Lipid Research, Vol. 42, 1913-1922, November 2001
Copyright © 2001 by Lipid Research, Inc.
Immune complexes and IFN- decrease cholesterol 27-hydroxylase in human arterial endothelium and macrophages
Allison B. Reissa,
Nahel W. Awadallaha,
Sandeep Malhotraa,
M. Carmen Montesinosa,
Edwin S. L. Chana,
Norman B. Javitta, and
Bruce N. Cronsteina
a Department of Medicine, New Bellevue 16N28, New York University School of Medicine, 550 First Avenue, New York, NY 10016
Correspondence to:
Allison B. Reiss, To whom correspondence should be addressed., reissa01{at}popmail.med.nyu.edu (E-mail)
The enzyme cholesterol 27-hydroxylase, expressed by arterial endothelium and monocytes/macrophages, is one of the first lines of defense against the development of atherosclerosis. By catalyzing the hydroxylation of cholesterol to 27-hydroxycholesterol, which is more soluble in aqueous medium, the enzyme promotes the removal of cholesterol from the arterial wall. Prior studies have suggested that immune reactants play a role in the pathogenesis of atherosclerosis; we report here that immune reactants, IFN- and immune complexes bound to C1q, but not interleukin-1 and tumor necrosis factor, diminish the expression of cholesterol 27-hydroxylase in human aortic endothelial cells, peripheral blood mononuclear cells, monocyte-derived macrophages, and the human monocytoid cell line THP-1. In addition, our studies demonstrate that immune complexes down-regulate cholesterol 27-hydroxylase only after complement fixation via interaction with the 126-kD C1qRp protein on endothelial cells and THP-1 cells.
These results are consistent with the prior demonstration that IFN- contributes to the pathogenesis of atherosclerosis and suggest a role for C1q receptors in the atherogenic process. Moreover, these observations suggest that one mechanism by which immune reactants contribute to the development of atherosclerosis is by down-regulating the expression of the enzymes required to maintain cholesterol homeostasis in the arterial wall. Reiss, A. B., N. W. Awadallah, S. Malhotra, M. C. Montesinos, E. S. L. Chan, N. B. Javitt, and B. N. Cronstein. Immune complexes and IFN- decrease cholesterol 27-hydroxylase in human arterial endothelium and macrophages. J. Lipid Res. 2001. 42: 19131922.
Supplementary key words:
atherosclerosis, complement 1q, cytokines, 27-hydroxycholesterol

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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
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