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BioMed Research International
Volume 2014 (2014), Article ID 312647, 8 pages
http://dx.doi.org/10.1155/2014/312647
Research Article

Infliximab Reverses Suppression of Cholesterol Efflux Proteins by TNF-α: A Possible Mechanism for Modulation of Atherogenesis

Winthrop Research Institute and Division of Rheumatology, Allergy and Immunology, Department of Medicine, Winthrop-University Hospital, 222 Station Plaza North, Suite 502, Mineola, NY 11501, USA

Received 20 April 2013; Revised 29 October 2013; Accepted 30 October 2013; Published 23 January 2014

Academic Editor: Marija Mostarica-Stojković

Copyright © 2014 Iryna Voloshyna et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Tumor necrosis factor- (TNF-) α is a proinflammatory proatherogenic cytokine. Infliximab, an anti-TNF-α monoclonal antibody, is effective in treating rheumatoid arthritis. However, its impact on cardiovascular burden and lipid transport is unclear. The present study investigates the effect of TNF-α and infliximab on reverse cholesterol transport (RCT) proteins. Uptake of modified lipoproteins by macrophages in the vasculature leads to atherogenic foam cell formation. RCT is mediated by proteins including ATP binding cassette transporters A1 (ABCA1), G1 (ABCG1), liver X receptor- (LXR-) α, and 27-hydroxylase. RCT counteracts lipid overload by ridding cells of excess cholesterol. THP-1 human monocytes were incubated with either TNF-α alone or TNF-α with infliximab. Expression of proteins involved in cholesterol efflux was analyzed. TNF-α significantly reduced both ABCA1 and LXR-α mRNA (to , , and , , versus control set as 100%, resp.). Infliximab nullified the TNF-α effect. Results were confirmed by Western blot. Infliximab abolished the increase in foam cells induced by TNF-α. TNF-α treatment significantly reduces ABCA1 and LXR-α expression in monocytes, thus bringing about a proatherogenic state. The anti-TNF drug infliximab, commonly used in rheumatology, restored RCT proteins. This is the first report of an atheroprotective effect of infliximab on RCT in monocytes.