SM934 Treated Lupus-Prone NZBxNZW F.sub.1 Mice by Enhancing Macrophage Interleukin-10 Production and Suppressing Pathogenic T Cell Development

Artemisinin and its derivatives were reported to possess strong regulatory effects on inflammation and autoimmune diseases. This study was designed to examine the therapeutic effects and underlying mechanisms of SM934, a water-soluble artemisinin analogue, on lupus-prone female NZBxNZW F.sub.1 mice....

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Published in:PloS one 2012-02, Vol.7 (2), p.e32424
Main Authors: Hou, Li-Fei, He, Shi-Jun, Li, Xin, Wan, Chun-Ping, Yang, Yang, Zhang, Xiao-Hui, He, Pei-Lan, Zhou, Yu, Zhu, Feng-Hua, Yang, Yi-Fu, Li, Ying, Tang, Wei, Zuo, Jian-Ping
Format: Article
Language:English
Subjects:
Albumin
B cells
Biological response modifiers
Health aspects
House mouse
Immunoglobulin G
Inflammation
Interferon
Interleukins
Lupus
Macrophages
Medical research
T cells
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Summary:Artemisinin and its derivatives were reported to possess strong regulatory effects on inflammation and autoimmune diseases. This study was designed to examine the therapeutic effects and underlying mechanisms of SM934, a water-soluble artemisinin analogue, on lupus-prone female NZBxNZW F.sub.1 mice. NZB/W F.sub.1 mice were treated orally with SM934 for 3 or 6 months respectively to investigate the effect on clinical manifestations and immunological correlates. To further explore the mechanisms of SM934, ovalbumin (OVA)-immunized or interferon (IFN)-[gamma]-elicited C57BL/6 mice were used. In vivo, treatment with SM934 for 3 or 6 months significantly delayed the progression of glomerulonephritis and increased the survival rate of NZB/W F.sub.1 mice. Clinical improvement was accompanied with decreased Th1-related anti-double-strand DNA (dsDNA) IgG2a and IgG3 Abs, serum interleukin (IL)-17, and increased Th2-related anti-dsDNA IgG1 Ab, serum IL-10 and IL-4. SM934 treatment also suppressed the accumulation of effector/memory T cells, induced the apoptosis of CD4.sup.+ T cells, while enhancing the development of regulatory T cells in NZB/W F.sub.1 mice. In addition, SM934 treatment promoted the IL-10 production of macrophages from NZB/W F.sub.1 mice, OVA-immunized C57BL/6 mice and IFN-[gamma]-elicited C57BL/6 mice. In vitro, SM934 enhanced IL-10 production from primary macrophages stimulated with IFN-[gamma]. The results of this study demonstrated that artemisinin analogue SM934 had therapeutic effects on lupus-prone female NZB/W F.sub.1 mice by inhibiting the pathogenic helper T cell development and enhancing anti-inflammatory cytokine IL-10 production.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0032424