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.