Pharmacological repression of RORγ is therapeutic in the collagen-induced arthritis experimental model (P5214)
| Autor: | Mi Ra Chang, Brent Lyda, Theodore Kamenecka, Patrick Griffin |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:212.4-212.4 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The nuclear receptor RORγ has been shown to play an essential role in the development of Th17 cells. Previously, it was reported that the potent and selective RORγ inverse agonist SR2211 was effective at modulating RORγ activity in cell culture. More recently we demonstrated that the RORγ inverse agonist SR2211 can repress expression and production inflammatory cytokines in Th17 cells and LPS stimulated RAW264.7 cells. Here we present in vivo efficacy of SR2211 in an experimental model of arthritis, the murine collagen induced arthritis or CIA model. Significantly reduced Joint CIA scores were observed in SR2211 treated mice as compared with vehicle in the acute phase of the model. CIA represents an autoimmune environment characterized by the accumulation of inflammatory cells into the synovium leading to the destruction of joints. In this model cytokines have been shown to be important regulators of synovial inflammation. Administration of SR2211 in CIA mice led to an increase in IFNγ in ex vivo stimulated draining lymph nodes. As IFNγ has been shown to be beneficial for the treatment of rheumatoid arthritis. In previous work, patients treated with IFNγ showed significant therapeutic potential of RA the data presented suggest the potential of targeting RORγ to repress inflammatory T cell function and macrophage activation in arthritis. Thus, SR2211 has potential utility in the treatment of inflammatory disease. |
| Databáze: | OpenAIRE |
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