[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.

CONCLUSION:

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: Feng-ming Luo, Chun-tao Liu, Shuang-qing Li, Zeng-li Wang
• Journal: Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases (Zhonghua Jie He He Hu Xi Za Zhi) Vol. 28 Issue 5 Pg. 320-3 (May 2005) ISSN: 1001-0939 [Print] China
• PMID: 15949312 (Publication Type: English Abstract, Journal Article)

Chemical References

• Simvastatin

Topics

• Adult
• Apoptosis (drug effects)
• Asthma (diagnosis)
• Cells, Cultured
• Eosinophils (cytology, drug effects)
• Female
• Humans
• Male
• Simvastatin (pharmacology)
• Young Adult