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- Title
The new water-soluble artemisinin derivative SM905 ameliorates collagen-induced arthritis by suppression of inflammatory and Th17 responses.
- Authors
Wang, J.-X.; Tang, W.; Zhou, R.; Wan, J.; Shi, L.-P.; Zhang, Y.; Yang, Y.-F.; Li, Y.; Zuo, J.-P.
- Abstract
<bold>Background and Purpose: </bold>Our previous study showed that SM905, a novel artemisinin derivative, exhibited potent immunosuppressive activity. In this study, we evaluate preventive and therapeutic effect of SM905 on collagen-induced arthritis (CIA) in DBA/1 mice, and investigate its mechanisms both in inflammatory and autoimmune aspects of the disease.<bold>Experimental Approach: </bold>CIA was induced by type II bovine collagen (CII) in DBA/1 mice. SM905 was given orally either before (continuously 1 day before booster immunization) or after disease onset (continuously 14 days after booster immunization). Disease incidence and severity were monitored, mRNA expression of proinflammatory mediators was determined by real-time PCR, purified T cell proliferation was assessed using [(3)H]-thymidine incorporated assay, and T helper (Th) 17/Th1/Th2 type cytokine production was examined by ELISA.<bold>Key Results: </bold>Oral treatment with SM905 delayed disease onset, reduced arthritis incidence and severity, and suppressed the enhanced expression of pro-inflammatory cytokines, chemokines and chemokine receptors in draining lymph nodes. The CII-induced T cell proliferation and production of interleukin (IL)-17A by T cells were strikingly inhibited. Correspondingly, the mRNA expression of IL-17A and RORgamma t (a specific transcription factor for Th17) was also reduced. This effect was coupled with a striking reduction of IL-6 production, which has a critical role in Th17 development. In established arthritis, SM905 profoundly inhibited disease progression, reduced IL-17A and RORgamma t mRNA expression, and suppressed pro-inflammatory mediator expression in arthritic joints.<bold>Conclusions and Implications: </bold>SM905 had beneficial effects on CIA by suppressing inflammatory and pathogenic Th17 responses.
- Subjects
ARTEMISININ; ANTIMALARIALS; PEROXIDES; ARTHRITIS; PHARMACOLOGY; RNA metabolism; DRUG therapy for arthritis; BIOLOGICAL models; INTERLEUKINS; COLLAGEN; DISEASE progression; RESEARCH; CATTLE; ANIMAL experimentation; RESEARCH methodology; ARTHRITIS Impact Measurement Scales; LYMPH nodes; CELL receptors; CELL physiology; RNA; MEDICAL cooperation; EVALUATION research; SEVERITY of illness index; COMPARATIVE studies; GENES; T cells; CHEMOKINES; MICE; PHARMACODYNAMICS
- Publication
British Journal of Pharmacology, 2008, p1303
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/bjp.2008.11