Abstract
Retinoic acid receptor-related orphan receptor-alpha (RORalpha) is a nuclear orphan receptor. Adenovirus-mediated overexpression of RORalpha1 and RORalpha4 suppressed tumor necrosis factor-alpha (TNF-alpha)-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 RORalpha1 and RORalpha4 also suppressed TNF-alpha-stimulated translocation of p50 and p65 to the nucleus. In contrast, dominant-negative deletion mutants of RORalpha1 and RORalpha4 failed to suppress the induction of VCAM-1 and ICAM-1 and translocations of p50 and p65. These results suggest that RORalpha1 and RORalpha4 regulate the inflammatory responses via inhibition of the nuclear factor-kappaB signaling pathway in endothelial cells.
MeSH terms
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Animals
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Cell Line
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Cells, Cultured
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DNA Primers
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Endothelium, Vascular / physiology*
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics*
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Genes, Reporter
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Humans
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Intercellular Adhesion Molecule-1 / genetics*
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Luciferases / genetics
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Nuclear Receptor Subfamily 1, Group F, Member 1
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Receptor Protein-Tyrosine Kinases
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Receptor Tyrosine Kinase-like Orphan Receptors
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Receptors, Cell Surface / genetics*
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Receptors, Cytoplasmic and Nuclear
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Reverse Transcriptase Polymerase Chain Reaction
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Trans-Activators
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Transfection
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Tumor Necrosis Factor-alpha / pharmacology*
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Umbilical Veins
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Vascular Cell Adhesion Molecule-1 / genetics*
Substances
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DNA Primers
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Nuclear Receptor Subfamily 1, Group F, Member 1
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RORA protein, human
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Receptors, Cell Surface
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Receptors, Cytoplasmic and Nuclear
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Trans-Activators
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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Luciferases
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ROR1 protein, human
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Receptor Protein-Tyrosine Kinases
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Receptor Tyrosine Kinase-like Orphan Receptors