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Indirubin inhibits the migration, invasion, and activation of fibroblast-like synoviocytes from rheumatoid arthritis patients

Abstract

Objectives

To evaluate the inhibition of indirubin in FLSs migration, invasion, activation, and proliferation in RA FLSs.

Methods

The levels of IL-6 and IL-8 in cultural supernatants were measured by ELISA. RA FLS migration and invasion in vitro were measured by the Boyden chamber method and the scratch assay. Signal transduction protein expression was measured by western blot. FLS proliferation was detected by Edu incorporation. F-actin was measured by immunofluorescence staining.

Results

We found that indirubin reduced migration, invasion, inflammation, and proliferation in RA FLSs. In addition, we demonstrated that indirubin inhibited lamellipodium formation during cell migration. To gain insight into molecular mechanisms, we evaluated the effect of indirubin on PAK1 and MAPK activation. Our results indicated that indirubin inhibited the activity of PAK1 and MAPK.

Conclusions

Our observations suggest that indirubin may be protective against joint destruction in RA by regulating synoviocyte migration, invasion, activation, and proliferation.

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Acknowledgements

The authors would like to thank Jinjin Fan for her technical assistance.

Funding

This work is supported by grants from Guangdong Project of Science and Technology (Grant Number 2012B031800375).

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Corresponding author

Correspondence to Liuqin Liang.

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Conflict of interest

No conflict of Interest has been declared by authors.

Additional information

Mingcheng Huang, Lihui Wang, and Shan Zeng contributed equally to this work.

Responsible Editor: Liwu Li.

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Huang, M., Wang, L., Zeng, S. et al. Indirubin inhibits the migration, invasion, and activation of fibroblast-like synoviocytes from rheumatoid arthritis patients. Inflamm. Res. 66, 433–440 (2017). https://doi.org/10.1007/s00011-017-1027-5

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  • DOI: https://doi.org/10.1007/s00011-017-1027-5

Keywords

  • Indirubin
  • Fibroblast-like synoviocytes
  • Migration
  • Inflammation
  • MAPK
  • PAK1