The New Water-soluble Artemisinin Derivative SM905 Ameliorates Collagen-induced Arthritis by Suppression of Inflammatory and Th17 Responses

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2008 Feb 12

PMID 18264129

Citations 31

Authors

J-X Wang

W Tang

R Zhou

J Wan

L-P Shi

Y Zhang

Y-F Yang

Y Li

J-P Zuo

Affiliations

Soon will be listed here.

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.

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