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Oral antigens induce rheumatoid arthritis-like inflammation in a rat model

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Abstract

Background and aims

The pathogenesis of rheumatoid arthritis (RA) is to be further elucidated. The present study aims to investigate the role of oral antigen in the induction of RA-like inflammation in the articular joints of rats.

Methods

An RA animal model was developed by gavage-feeding with antigen and aspirin, and lipopolysaccharide intraperitoneal injection. The gut epithelial barrier function was assessed by the absorption of mannitol and lactose. The absorption of the specific antigen was observed by the immune fluorescent method. The frequency of antigen specific CD4+ T cells in the peripheral system was assessed by flow cytometry. The inflammation in the ankle joints was evaluated by light microscopy and immunohistochemistry.

Results

Rats treated with aspirin showed intestinal barrier dysfunction; high contents of the specific antigen were absorbed into the lamina propria. The antigen specific CD4+ T cells were detected in the spleen that could be activated by exposure to the specific antigen as well as the extracts of joint tissue. High levels of proinflammatory cytokines were detected in the sera. Antigen specific immune complexes were localized in the ankle joints. Heavy extravasation was observed in the synovial cavity. The histology showed an inflammatory feature in the ankle joints.

Conclusions

Oral antigen can induce RA-like inflammation in the articular joints under certain environment such as gut epithelial barrier dysfunction.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation (No. 30871752, 31101280), Postdoctoral Scholarship of China (No. 20060390196), Shenzhen-Hong Kong Scientific Invention Foundation (CX Q2008026), Shenzhen Municipal Key Research Laboratory Support (SW201110010). Canadian Institutes of Health Research (CIHR; #191063, #177843 and #220058), Natural Sciences and Engineering Research Council of Canada (#371268).

Conflict of interest

The authors do not have any conflict of interests to declare.

Author information

Authors and Affiliations

  1. Institute of Allergy and Immunology, Shenzhen University, Shenzhen, China

    Dandan Wu, Xiaoyu Liu, Hong Su, Dongsheng Hu, Zhong Huang & Zhigang Liu

  2. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada

    Xiao Chen & Ping-Chang Yang

  3. Department of Pathophysiology, Hainan Medical College, Haikou, China

    Huiyun Zhang

Authors
  1. Dandan Wu
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  2. Xiaoyu Liu
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  3. Hong Su
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  4. Xiao Chen
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  5. Huiyun Zhang
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  6. Dongsheng Hu
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  7. Zhong Huang
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  8. Ping-Chang Yang
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  9. Zhigang Liu
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Corresponding authors

Correspondence to Ping-Chang Yang or Zhigang Liu.

Additional information

Responsible Editor: John Di Battista.

D. Wu, X. Liu and H. Su are contributed equally to this work.

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Wu, D., Liu, X., Su, H. et al. Oral antigens induce rheumatoid arthritis-like inflammation in a rat model. Inflamm. Res. 62, 291–297 (2013). https://doi.org/10.1007/s00011-012-0577-9

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  • DOI: https://doi.org/10.1007/s00011-012-0577-9

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