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Triptolide Inhibits Expression of Inflammatory Cytokines and Proliferation of Fibroblast-like Synoviocytes Induced by IL-6/sIL-6R-Mediated JAK2/STAT3 Signaling Pathway

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Summary

Triptolide, a component of the Chinese herb Tripterygium wilfordii Hook F, has been proved to be effective in the treatment of rheumatoid arthritis (RA). However, its underlying mechanisms on RA have not yet been well established. We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes (FLS) induced by the complex of interleukin-6 (IL-6) and the soluble form of the IL-6 receptor (sIL-6R). Furthermore, to clarify the underlying mechanisms, we treated FLS with the Janus-activated kinase 2 (JAK2) inhibitor/signal transducer and activator of transcription 3 (STAT3) activation blocker AZD1480. In this study, immunohistochemical staining was used to identify vimentin (+) and CD68 (−) in FLS. The FLS proliferation was measured by cell proliferation assay, and the cell cycles were analyzed by flow cytometry. Furthermore, ELISA was used to detect the expression of the inflammatory factors in culture solution. The expression levels of p-JAK2, JAK2, p-STAT3 and STAT3 were investigated through Western blotting analysis. The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines, including IL-6, interleukin-1β (IL-1β) and vascular endothelial growth factor (VEGF). Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3. The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway. It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.

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Author notes

  1. The authors contributed equally to this study.

Authors and Affiliations

  1. National & Local Joint Engineering Research Center of Orthopaedic Biomaterials, Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, 518000, China

    Jian-jing Lin, Hui Zeng, De-li Wang & Jian Weng

  2. Arthritis Clinical and Research Center, Peking University People’s Hospital, Beijing, 100044, China

    Jian-jing Lin & Ke Tao

  3. Department of Rheumatism and Immunology, Peking University Shenzhen Hospital, Shenzhen, 518000, China

    Nan Gao

  4. Department of Radiology, Peking University Shenzhen Hospital, Shenzhen, 518000, China

    Jun Yang

Authors
  1. Jian-jing Lin
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  2. Ke Tao
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  3. Nan Gao
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  4. Hui Zeng
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  5. De-li Wang
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  6. Jun Yang
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  7. Jian Weng
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Corresponding authors

Correspondence to Jun Yang or Jian Weng.

Additional information

This study was supported by grants from the Shenzhen City Science and Technology Bureau of China (No. JCYJ20170307111755218) and “San-Ming” Project of Medicine in Shenzhen (No. SZSM201612092).

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Lin, Jj., Tao, K., Gao, N. et al. Triptolide Inhibits Expression of Inflammatory Cytokines and Proliferation of Fibroblast-like Synoviocytes Induced by IL-6/sIL-6R-Mediated JAK2/STAT3 Signaling Pathway. CURR MED SCI 41, 133–139 (2021). https://doi.org/10.1007/s11596-020-2302-1

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  • DOI: https://doi.org/10.1007/s11596-020-2302-1

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