Rev-erbalpha upregulates NF-kappaB-responsive genes in vascular smooth muscle cells.
Rev-erbalpha and retinoic acid receptor-related orphan receptor-alpha (RORalpha) are orphan nuclear receptors but their effects on transcription are opposed. Here, we show that Rev-erbalpha was expressed predominantly in vascular smooth muscle cells (VSMCs) rather than endothelial cells. Overexpression of Rev-erbalpha upregulated the expression of interleukin-6 and cyclooxygenase-2, and increased transactivation by NF-kappaB and translocation of p65 to the nucleus in A7r5 VSMCs. Furthermore, the expression of Rev-erbalpha was upregulated by RORalpha1 but that upregulation was attenuated by Rev-erbalpha itself in A7r5 VSMCs. These results suggest a regulatory link between Rev-erbalpha and the NF-kappaB pathway.
Migita
Hideyuki
H
Cardiovascular Research, Drug Discovery Institute, Nihon Schering K.K., 1900-1, Togo Mobara, Chiba 297-0017, Japan. hmigita@schering.co.jp
Morser
John
J
Kawai
Kohichi
K
D001011:Aorta / Q000166:cytology; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis; D008565:Membrane Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D020239:Receptor Cross-Talk; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution; D015534:Trans-Activators / Q000502:physiology*; D051996:Transcription Factor RelA; D015533:Transcriptional Activation; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; C064353:NR1D1 protein, human; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases