The new water-soluble artemisinin derivative SM905 ameliorates collagen-induced arthritis by suppression of inflammatory and Th17 responses
Language: 
English
Abstract: 

BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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. CONCLUSIONS AND IMPLICATIONS: SM905 had beneficial effects on CIA by suppressing inflammatory and pathogenic Th17 responses.

Author(s): 
Wang, J.-X.
Tang, W.
Zhou, R.
Wan, J.
Shi, L.-P.
Zhang, Y.
Yang, Y.-F.
Li, Y.
Zuo, J.-P.
Item Type: 
Journal Article
Publication Title: 
British Journal of Pharmacology
Journal Abbreviation: 
Br. J. Pharmacol.
Publication Date: 
3/8/2015
Publication Year: 
2008
Pages: 
1303-1310
Volume: 
153
Issue: 
6
ISSN: 
0007-1188
DOI: 
10.1038/bjp.2008.11
Library Catalog: 
PubMed
Extra: 
PMID: 18264129 PMCID: PMC2275452

Turabian/Chicago Citation

J.-X. Wang, W. Tang, R. Zhou, J. Wan, L.-P. Shi, Y. Zhang, Y.-F. Yang, Y. Li and J.-P. Zuo. 3/8/2015. "The new water-soluble artemisinin derivative SM905 ameliorates collagen-induced arthritis by suppression of inflammatory and Th17 responses." British Journal of Pharmacology 153: 6: 1303-1310. 10.1038/bjp.2008.11.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1038/bjp.2008.11 | issn = 0007-1188 | volume = 153 | pages = 1303-1310 | last = Wang | first = J.-X. | coauthors = Tang, W., Zhou, R., Wan, J., Shi, L.-P., Zhang, Y., Yang, Y.-F., Li, Y., Zuo, J.-P. | title = The new water-soluble artemisinin derivative SM905 ameliorates collagen-induced arthritis by suppression of inflammatory and Th17 responses | journal = British Journal of Pharmacology | date = 3/8/2015 | pmid = | pmc = }} </ref>