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A plant-derived ligand favoring monomeric glucocorticoid receptor conformation with impaired transactivation potential attenuates collagen-induced arthritis.
J Immunol ; 180(4): 2608-15, 2008 Feb 15.
Article en En | MEDLINE | ID: mdl-18250472
The glucocorticoid receptor (GR) is a transcription factor regulating its target genes either positively, through direct binding to the promoter of target genes, or negatively by the interference with the activity of transcription factors involved in proinflammatory gene expression. The well-known adverse effects of glucocorticoids are believed to be mainly caused by their GR-mediated gene-activating properties. Although dimerization of GR is thought to be essential for gene-activating properties, no compound has yet been described which selectively imposes GR monomer formation and interference with other transcription factors. In the present study, we report on a GR-binding, plant-derived compound with marked dissociative properties in rheumatoid arthritis fibroblast-like synoviocytes, which are important effector cells in inflammation and matrix degradation in rheumatoid arthritis. In addition, these findings could be extended in vivo in murine collagen-induced arthritis, in which joint inflammation was markedly inhibited without inducing hyperinsulinemia. Therefore, we conclude that GR monomers are sufficient for inhibition of inflammation in vivo.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Extractos Vegetales / Receptores de Glucocorticoides / Transactivadores / Salsola / Etilaminas / Acetatos Idioma: En Revista: J Immunol Año: 2008 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Experimental / Extractos Vegetales / Receptores de Glucocorticoides / Transactivadores / Salsola / Etilaminas / Acetatos Idioma: En Revista: J Immunol Año: 2008 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Estados Unidos