title: [Simvastatin induces eosinophil apoptosis in vitro].
abstract: OBJECTIVE
  To investigate the effect of simvastatin, a 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitor, on eosinophils (EOSs) apoptosis in asthma patients.
  
  
  METHODS
  Peripheral blood EOSs from 10 asthma patients were cultured in the presence or absence of simvastatin (1, 5, 10, 20 micromol/L), together with or without mevalonate (100 micromol/L) for 6, 12, 24, and 48 h. Apoptosis was monitored by annexin V/PI staining and flow cytometry. Caspase-3 was measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  EOSs were particularly susceptible to apoptosis after incubated with 5 micromol/L simvastatin for 6, 12, 24, and 48 h [the rates of EOSs undergoing apoptosis were: (23 +/- 3)%, (24 +/- 3)%, (41 +/- 6)%, (70 +/- 12)% in control and (32 +/- 4)%, (47 +/- 7)%, (62 +/- 9)%, (86 +/- 14)% in simvastatin; compared with control at the same time point: P = 0.000]. EOS apoptosis occurred at doses of 1 micromol/L and was already maximal at 5 micromol/L after incubated with simvastatin for 12 h [the rates of EOSs undergoing apoptosis were: (24 +/- 3)% in control, (37 +/- 3)%, (51 +/- 3)%, (53 +/- 4)%, (52 +/- 4)% in 1, 5, 10, 20 micromol/L simvastatin, respectively; compared with control: P = 0.000]. The level of caspase-3 in EOSs was consistent with the rate of cell apoptosis [(8 +/- 3) microg/L in control, (14 +/- 4), (22 +/- 4), (24 +/- 4), (23 +/- 5) microg/L in 1, 5, 10, 20 micromol/L simvastatin, respectively; compared with control: P = 0.000 - 0.003]. However, Co-incubation of simvastatin with mevalonate (the production of HMGR) completely reversed the activity of simvastatin on EOS apoptosis even when the highest simvastatin (20 micromol/L) dose was used; the rates of EOSs undergoing apoptosis in the control, mevalonate plus simvastatin and simvastatin alone were (24 +/- 3)%, (52 +/- 4)% and (25 +/- 3)%, respectively; while the caspase-3 levels were (8 +/- 3) microg/L, (23 +/- 5) microg/L and (9 +/- 3) microg/L, respectively.
  
  
  CONCLUSIONS
  Simvastatin induces apoptosis of EOSs in asthma patients via its ability to block the synthesis of the important isoprenoid intermediates, which leads to the inhibition of small GTP-binding protein activity.
authors.affiliation: Department of Golden, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Feng-ming
authors.initials: FM
authors.lastname: Luo
authors.forename: Chun-tao
authors.initials: CT
authors.lastname: Liu
authors.forename: Shuang-qing
authors.initials: SQ
authors.lastname: Li
authors.forename: Zeng-li
authors.initials: ZL
authors.lastname: Wang
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000175:diagnosis; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D019821:Simvastatin / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D019821:Simvastatin