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

FEBS Letters

Migita, Hideyuki²  Satozawa, Noboru²  Kawai, Kohichi²  Lin, Jiing-Huey¹  Morser, John¹ 

[1] Cardiovascular Research, Berlex Biosciences, Richmond, CA 94804, USA;Cardiovascular Research, Drug Discovery Institute, Nihon Schering K.K., 1900-1, Togo Mobara, Chiba 297-0017, Japan

关键词: Nuclear receptor;    Endothelial cell;    Vascular cell adhesion molecule-1;    Intracellular adhesion molecule-1;    Nuclear factor-κB;    Activator protein-1;    AP-1;    activator protein-1;    DBD;    DNA-binding domain;    HUVECs;    human umbilical vein endothelial cells;    ICAM-1;    intracellular adhesion molecule-1;    LBD;    ligand-binding domain;    NF-κB;    nuclear factor-κB;    RORα;    retinoic acid receptor-related orphan receptor-α;    RORE;    ROR response element;    TNF-α;    tumor necrosis factor-α;    VCAM-1;    vascular cell adhesion molecule-1;    VSMCs;    vascular smooth muscle cells;   

DOI  :  10.1016/S0014-5793(03)01502-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown