RORα1 and RORα4 suppress TNF-α-induced VCAM-1 and ICAM-1 expression in human endothelial cells

Abstract
Retinoic acid receptor-related orphan receptor-α (RORα) is a nuclear orphan receptor. Adenovirus-mediated overexpression of RORα1 and RORα4 suppressed tumor necrosis factor-α (TNF-α)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells. Overexpression of RORα1 and RORα4 also suppressed TNF-α-stimulated translocation of p50 and p65 to the nucleus. In contrast, dominant-negative deletion mutants of RORα1 and RORα4 failed to suppress the induction of VCAM-1 and ICAM-1 and translocations of p50 and p65. These results suggest that RORα1 and RORα4 regulate the inflammatory responses via inhibition of the nuclear factor-κB signaling pathway in endothelial cells

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