RORalpha1 and RORalpha4 suppress TNF-alpha-induced VCAM-1 and ICAM-1 expression in human endothelial cells.
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.
Migita
Hideyuki
H
Cardiovascular Research, Drug Discovery Institute, Nihon Schering KK, 1900-1, Togo Mobara, Chiba 297-0017, Japan. migitabb@yahoo.co.jp
Satozawa
Noboru
N
Lin
Jiing-Huey
JH
Morser
John
J
Kawai
Kohichi
K
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D017930:Genes, Reporter; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011956:Receptors, Cell Surface / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
D017931:DNA Primers; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D008156:Luciferases; C078716:ROR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors