Simvastatin inhibits the proliferation of HL-60 clone 15- derived eosinophils by inducing the arrest of the cell cycle in the G1/S phase

Chia Hsiang Fu, Ta Jen Lee, Chi Che Huang, Po Hung Chang, Jung Wei Tsai, Li Pang Chuang*, Jong Hwei Su Pang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations

Abstract

Eosinophils and their granular proteins are crucial for combating allergic airway diseases. Eosinophils derived from HL-60 clone 15 (HC15) cells have been established as a feasible alternative cell model for human primary eosinophils. Simvastatin, a cholesterol-lowering agent, has been shown to exhibit anti-inflammatory and anti-allergic effects. Among the granular eosinophil proteins, eosinophil cationic protein (ECP) is the one best recognised in allergic airway diseases. The aim of our study is to investigate the effect and regulatory mechanisms of simvastatin on ECP levels derived from eosinophils. Both HC15 cell counts and ECP levels decreased after simvastatin treatment in the animal and cell models; however, after a cell count adjustment, simvastatin was not observed to exert a significantly inhibitory effect on ECP expression. Real-time polymerase chain reaction and Western blotting analyses demonstrated that simvastatin did not inhibit the intracellular formation or release of ECP. Cell cycle analysis showed that the percentage of HC15 cells in the G1 and S phases significantly increased and decreased, respectively, after simvastatin treatment. Simvastatin inhibited the proliferation of HC15-derived eosinophils by inducing G1/S cell cycle arrest in a dose-dependent manner. Its effect on the cell cycle involved the downregulation of cyclin A but without the presence of mevalonate; therefore, total ECP expression from eosinophils decreased, not by suppressing the actual formation or release of ECP but by arresting the G1/S cell cycle phase and inhibiting subsequent cell proliferation through the mevalonate pathway.

Original languageEnglish
Article number172400
JournalEuropean Journal of Pharmacology
Volume856
DOIs
StatePublished - 05 08 2019

Bibliographical note

Publisher Copyright:
© 2019

Keywords

  • Cell cycle
  • ECP
  • Eosinophil
  • Eosinophil cationic protein
  • HL-60
  • Simvastatin

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