[Simvastatin induces eosinophil apoptosis in vitro].
Zhonghua Jie He He Hu Xi Za Zhi
; 28(5): 320-3, 2005 May.
Article
en Zh
| MEDLINE
| ID: mdl-15949312
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Asma
/
Apoptosis
/
Simvastatina
/
Eosinófilos
Tipo de estudio:
Diagnostic_studies
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
Zh
Revista:
Zhonghua Jie He He Hu Xi Za Zhi
Año:
2005
Tipo del documento:
Article
País de afiliación:
China