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Abstract
Context: Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases.
Objective: Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases.
Materials and methods: In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration.
Results: In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p < 0.0001). Also, we found that meisoindigo did not affect the process of leukocyte reverse migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway.
Discussion and conclusion: Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.
Acknowledgements
We thank Prof. Zhu Chen and Prof. Saijuan Chen for their kind support and guidance on this work. We thank Dr. Liu Ping for providing compounds including arsenic trioxide, indirubin and tanshinone IIA.
Disclosure statement
The authors report no declarations of interest.
Funding
This work was supported by the National Natural Science Foundation of China for Excellent Young Scholars Grant [No. 81222004 to Yueying Wang], the Fundamental Research Funds for the Central Universities [No. 2042016kf0078 to Baixin Ye], and the Hubei Province Natural Science Foundation of China [No. 2015CFB350 to Xiang Gao].