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Jieduquyuziyin prescription suppresses IL-17 production and Th17 activity in MRL/lpr mice by inhibiting expression of Ca2+/calmodulin-dependent protein kinase-4

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Abstract

Jieduquyuziyin prescription (JP) is a traditional Chinese medicinal (TCM) formula which has been demonstrated to be effective for systemic lupus erythematosus (SLE) treatment as an approved hospital prescription for many years in China. But its mechanism of action in combating this disease is largely unknown. Our previous studies showed that JP can slow disease progression without producing significant toxic side effects. We treated MRL/lpr mice with JP to ascertain if JP could improve SLE by the suppression of Ca2+/calmodulin-dependent protein kinase-4 (CaMK4) expression. We investigated the role of JP in a model of SLE in MRL/lpr mice, and identified the possible mechanism of action. Mice were divided randomly into four groups: control, model, and two treatment groups. Sections of renal tissue were stained with hematoxylin and eosin (H&E). Histopathologic changes in the kidney were evaluated by light microscopy. T-helper (Th)17 cells were analyzed by flow cytometry. mRNA levels of interleukin (IL)-17, CaMK4, and RORγt were measured by reverse transcription polymerase chain reaction (RT-PCR). CaMK4 expression was assessed by Western blotting. The results showed that the percentages of Th17, IL-17, and RORγt in mice treated with JP were decreased remarkably compared to the model group (p < 0.05). Interestingly, a high CaMK4 expression was observed in the SLE mice, which was inhibited by JP. These results suggest that CaMK4 activity was increased in T cells from MRL/lpr mice compared with the control group. Our findings support the conclusion that the effects of JP on MRL/lpr mice may involve the regulation of CaMK4 overexpression in MRL/lpr mice.

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Acknowledgments

We thank the Zhejiang Chinese Medical University College of Basic Medical Science for their excellent technical assistance. We would also like to express our gratitude to Zhejiang Chinese Medical University College of Life Science. This study was supported by grants from the National Natural Science Foundation of China (no. 81001515) and the Natural Science Foundation of Zhejiang Province (no. LY14H270014).

Conflict of interest

The authors declare that they have no competing financial interest.

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Authors and Affiliations

  1. Zhejiang Chinese Medical University College of Life Science, Hangzhou, China

    Bingjie Shui & Weibiao Xia

  2. Zhejiang Chinese Medical University College of Basic Medical Science, Hangzhou, China

    Chengping Wen & Xinghong Ding

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  1. Bingjie Shui
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  2. Weibiao Xia
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  3. Chengping Wen
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  4. Xinghong Ding
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Correspondence to Xinghong Ding.

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Shui, B., Xia, W., Wen, C. et al. Jieduquyuziyin prescription suppresses IL-17 production and Th17 activity in MRL/lpr mice by inhibiting expression of Ca2+/calmodulin-dependent protein kinase-4. J Nat Med 69, 349–357 (2015). https://doi.org/10.1007/s11418-015-0900-1

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  • DOI: https://doi.org/10.1007/s11418-015-0900-1

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