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Upregulated IRAK1 and IRAK4 promoting the production of IFN-γ and IL-17 in Behcet’s disease

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Abstract

Purpose

To investigate the expression and function of IRAK1 and IRAK4 involved in the development of Behcet’s disease.

Methods

Twenty-eight Behcet’s patients and thirty-two normal subjects were involved in this study. The mRNA levels of IRAK1 and IRAK4 from active Behcet’s patients, inactive Behcet’s patients and normal controls were detected using real-time quantitative PCR. CD4+T cells were extracted from peripheral blood mononuclear cells of active Behcet’s patients and normal controls. After coculturing IRAK1/4 inhibitor with CD4+T cells in the presence of rIL-18 protein or rIL-1β protein for 3 days, the proliferation of CD4+T cells was measured using a modified MTT assay. Meanwhile, the levels of IFN-γ and IL-17 were detected by enzyme-linked immunosorbent assay.

Results

The mRNA levels of IRAK1 and IRAK4 were both significantly increased in active Behcet’s patients compared with those of inactive Behcet’s patients and normal subjects. However, there was no difference of IRAK1 mRNA level or the IRAK4 mRNA level between the inactive Behcet’s patients and normal controls. After coculturing with IRAK1/4 inhibitor, the proliferation of the CD4+T cells was inhibited both in active Behcet’s patients and in normal controls. Meanwhile, the expression of IFN-γ and IL-17 was also suppressed by IRAK1/4 inhibitor both in active Behcet’s patients and in normal subjects.

Conclusion

The high mRNA levels of IRAK1 and IRAK4 were correlated with the development of Behcet’s disease, which suggested that IRAK1 and IRAK4 might participate in the pathogenesis of Behcet’s disease. The inhibitory function of IRAK1/4 inhibitor prompts that it may be a new therapeutic target for treating this blindness disease.

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Acknowledgements

This study was supported by National Natural Science Foundation Project Grant 81200679. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Ophthalmology, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, People’s Republic of China

    Min Sun & Jian Ye

  2. Chongqing Key Laboratory of Ophthalmology, Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Min Sun, Peizeng Yang & Yan Yang

Authors
  1. Min Sun
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  2. Peizeng Yang
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  3. Yan Yang
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  4. Jian Ye
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Correspondence to Min Sun or Jian Ye.

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All authors declare that he/she has no conflict of interest.

Ethical approval

All procedures performed in studies were in accordance with the ethical standards of the Ethics Committee of the Third Affiliated Hospital of the Third Military Medical University and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Cite this article

Sun, M., Yang, P., Yang, Y. et al. Upregulated IRAK1 and IRAK4 promoting the production of IFN-γ and IL-17 in Behcet’s disease. Int Ophthalmol 38, 1947–1953 (2018). https://doi.org/10.1007/s10792-017-0682-4

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  • DOI: https://doi.org/10.1007/s10792-017-0682-4

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