Abstract
Purpose: To study the influence of artemisinin derivative, SM934 on activation, proliferation, differentiation and antibody-secreting capacity of B cells of systemic lupus erythematosus (SLE) mice, and the underlying mechanism.
 Methods: Female MRL/lpr mice (n = 60) were randomly assigned to four groups of 15 mice each: SLE, 2.5 mg/kg SM934; 5 mg/kg SM934, and 10 mg/kg SM934 groups. Serum levels of interleukins 6, 10, 17 and 21 (IL-6, IL-17, IL-10 and IL-21) were determined. The secretions of immunoglobulins G and M (IgG and IgM) by B cells were determined. The population of B lymphocyte subtypes was determined flow cytometrically. The expressions of Blimp-1 and Bcl-6, Toll-like receptors 7 and 9 (TLR7 and TLR9) mRNAs were determined.
 Results: SLE-induced upregulation of serum IL-10, IL-6, IL-17 and IL-21 was significantly and dosedependently reduced following a 2-month treatment with SM934 (p < 0.01). Treatment with SM934 significantly and dose-dependently accentuated B cell germinal center B cell populations, but significantly and dose-dependently decreased the populations of plasma and activated B cells (p < 0.01). The splenic levels of IgG and IgM were decreased in a dose-dependent fashion after 8 weeks of treatment (p < 0.01). Artemisinin derivative SM934 decreased the expression of Blimp-1, and upregulated the expression of Bcl-6, both in a dose-dependent manner (p < 0.01). Moreover, SM934 decreased the mRNA expressions of TLR7 and TLR9 in a dose-based manner (p < 0.01).
 Conclusion: Artemisinin derivative SM934 mitigates LSE syndromes by suppressing the TLR-induced B-cell stimulation and plasma cell generation
Highlights
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects several organs and systems
Interleukin 10 (IL10) is an anti-inflammatory factor secreted by mononuclear macrophages, and it stimulates the proliferation of B cells, thereby promoting development of SLE
It has been reported that the number of B cells and germinal center B cells were significantly decreased, while the population activated plasma and B cells were significantly increased after treatment with SM934, leading to the conclusion that the increased number of plasma cells enhanced the antibody- secreting function of B cells [17,18]
Summary
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects several organs and systems. Four groups of mice were randomly assembled This was used to determine the expressions of Blimp-1 and Bcl-6. Quantitative real-time polymerase chain 8 weeks of treatment with SM934 (p < 0.01; reaction (qRT-PCR). This was used to determine the levels of expression of TLR7 and TLR9 mRNAs. Total RNAs were isolated from portions of spleen homogenate using Trizol reagent and assessed spectrophotometrically. Treatment with SM934 significantly and dosedependently elevated the population B cells and germinal center B cells, while it significantly and dose-dependently reduced the population of plasma and activated B cells (p < 0.01) The splenic levels of IgG and IgM were significantly and dose-dependently reduced after 8 weeks of treatment with SM934 (p < 0.01; Table 3).
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