Human lactoferrin suppresses TNF-α-induced intercellular adhesion molecule-1 expression via competition with NF-κB in endothelial cells

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-α-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-κB to a proximal NF-κB site in ICAM-1 promoter. This type of repression represents an additional mechanism for the action of Lf in regulation of gene expression.

► Lactoferrin (Lf) inhibits TNF-α-stimulated ICAM-1 expression in endothelial cells. ► Lf down-regulates TNF-α-stimulated ICAM-1 expression at the transcriptional level. ► Lf binds to the proximal NF-κB site in human ICAM-1 promoter in vitro and in vivo. ► Lf interferes with NF-κB for binding to the ICAM-1 promoter region.