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Schistosoma japonicum cystatin attenuates murine collagen-induced arthritis

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Abstract

Recombinant SjCystatin (rSjCystatin), a recombinant protein of Schistosoma japonicum cystatin, has been reported to have an effect on immunoregulation mediated by IL-10 induction. Rheumatoid arthritis (RA) is a common autoimmune inflammatory arthropathy, and recombinant immune-modulating drugs for RA treatment are under development. We aimed to study the putative immune regulation of rSjCystatin and its prophylactic/therapeutic effects on murine collagen-induced arthritis (CIA). CIA was induced in DBA/1 mice by inoculation with bovine collagen II (CII). rSjCystatin was administered prior or post development of CIA. The severity of CIA was assessed using established clinical and histopathological scoring systems. The incidence was also determined. The CII-specific antibodies in sera and cytokines in splenocyte culture supernatants were measured by ELISA. Th1/Th2/Th17 cells and Tregs development in splenocytes were monitored by flow cytometry. The inflammatory mediators in the diseased joint were semiquantitated by qPCR. Prophylactic injection of rSjCystatin attenuated paw clinical scores, incidence, and histopathology scores of joints in CIA mice. The arthritis-alleviative effects were closely associated with the augmentation of IL-4, IL-10, and collagen-specific IgG1, and with the distinct reduction of IFN-γ, collagen-specific IgG2a, and the marked decrease of proinflammatory cytokines IL-6, IL-17, and TNF-α and RANKL. The data indicate that rSjCystatin may prevent cartilage destruction and inflammation of joints in CIA mice. The effects are related to the inhibitory modulation of Th1 and Th17 and upregulation of Tregs and Th2 via a shift of cytokines profiling from Th1 to Th2 response.

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Acknowledgments

The work was funded by the National Science Foundation of China (No. 81171606) and Science Foundation of Anhui Province (No. 1308085MH124). We would like to thank Li He from the Department of Human Parasitology, Basic Medical School, Tongji Medical College of HUST for the gift of recombinant plasmid of SjCystatin.

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    1. Department of Pathogen Biology, Provincial Laboratory of Pathogen Biology and Key Laboratory of Zoonoses Anhui, Anhui Medical University, Hefei, 230022, China

      Fang Liu, Weisheng Cheng, Faustina Pappoe, Xiaodong Hu, Huiqin Wen, Qingli Luo, Shushu Wang, Yuanyuan Xie, Yuanhong Xu & Jilong Shen

    2. Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

      Weisheng Cheng, Yuanhong Xu & Jilong Shen

    3. Department of Blood Transfusion, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China

      Huiqin Wen

    4. Department of Laboratory Diagnosis, the Provincial Tumor Hospital of Anhui Medical University, Hefei, 230022, China

      Fang Deng

    5. Department of Pathogen Biology, Anhui Medical University, Hefei, 230022, China

      Yuanhong Xu & Jilong Shen

    6. Department of Clinical Laboratory Medicine, Anhui Medical University, Hefei, 230022, China

      Yuanhong Xu & Jilong Shen

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    Liu, F., Cheng, W., Pappoe, F. et al. Schistosoma japonicum cystatin attenuates murine collagen-induced arthritis. Parasitol Res 115, 3795–3806 (2016). https://doi.org/10.1007/s00436-016-5140-0

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