[HTML][HTML] The orphan nuclear receptor RORα is a negative regulator of the inflammatory response

P Delerive, D Monté, G Dubois, F Trottein… - EMBO …, 2001 - embopress.org
P Delerive, D Monté, G Dubois, F Trottein, J Fruchart‐Najib, J Mariani, JC Fruchart, B Staels
EMBO reports, 2001embopress.org
Retinoid‐related orphan receptor α (RORα)(NR1F1) is a member of the nuclear receptor
superfamily whose biological functions are largely unknown. Since staggerer mice, which
carry a deletion in the RORα gene, suffer from immune abnormalities, we generated an
adenovirus encoding RORα1 to investigate its potential role in control of the inflammatory
response. We demonstrated that RORα is expressed in human primary smooth‐muscle cells
and that ectopic expression of RORα1 inhibits TNFα‐induced IL‐6, IL‐8 and COX‐2 …
Abstract
Retinoid‐related orphan receptor α (RORα)(NR1F1) is a member of the nuclear receptor superfamily whose biological functions are largely unknown. Since staggerer mice, which carry a deletion in the RORα gene, suffer from immune abnormalities, we generated an adenovirus encoding RORα1 to investigate its potential role in control of the inflammatory response. We demonstrated that RORα is expressed in human primary smooth‐muscle cells and that ectopic expression of RORα1 inhibits TNFα‐induced IL‐6, IL‐8 and COX‐2 expression in these cells. RORα1 negatively interferes with the NF‐κB signalling pathway by reducing p65 translocation as demonstrated by western blotting, immunostaining and electrophoretic mobility shift assays. This action of RORα1 on NF‐κB is associated with the induction of IκBα, the major inhibitory protein of the NF‐κB signalling pathway, whose expression was found to be transcriptionally upregulated by RORα1 via a ROR response element in the IκBα promoter. Taken together, these data identify RORα1 as a potential target in the treatment of chronic inflammatory diseases, including atherosclerosis and rheumatoid arthritis.
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