Human lactoferrin suppresses TNF-alpha-induced intercellular adhesion molecule-1 expression via competition with NF-kappa B in endothelial cells

Abstract

Lactoferrin (Lf) is known to have anti-inflammatory activity, but the mechanisms of action by Lf remain to be elucidated. Here, we demonstrated that TNF-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1) was down-regulated by Lf in a DNA-binding dependent manner at transcriptional level in endothelial cells. Our results showed that Lf bound to a DNA region in the ICAM-1 promoter in vitro as well as in chromatin context. Lf inhibited binding of NF-kappa B to a proximal NF-kappa B site in ICAM-1 promoter. This type of repression represents an additional mechanism for the action of Lf in regulation of gene expression. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.