Pravastatin Sodium Inhibit The Expression And Activity Of Human Peripheral Blood Neutrophil Elastase Induced By Lipopolysaccharide

Background Neutrophil elastase(NE)is a serine proteinase presents in neutrophil astrocytic granules which released when the neutrophils exposed to various stimulus.They are involved in the phagocytosis and degradation of microorganisms and strongly bactericidal active.However,NE over-expression can result in the release of inflammatory cytokines from immune cells and airway epithelial cells.It also has the potential ability to degrade elastin,basement membrane protein,and interstitial collagen,induce mucin over-production and goblet cell metaplasia.Airway obstruction is caused by high secretion of mucus in the airway.NE is overactive,which damages epithelial cells and reduces cilia function in vitro.NE is also thought to induce airway epithelial fibrosis.NE plays an important role in the development of lung infection and chronic inflammatory diseases.Pravastatin sodium is one of the statins.The anti-inflammatory effect of pravastatin in pulmonary inflammatory diseases has been reported in many animal and clinical studies.However,it is not clear whether statins inhibit the activation and excessive release of neutrophil elastase.Objective To study the effect of pravastatin sodium on the release and activity of neutrophil elastase(NE)induced by lipopolysaccharide(LPS)in human peripheral blood neutrophil.Methods Human peripheral blood neutrophils were isolated and cultured by Ficoll density gradient centrifugation,neutrophils and endophil granules were identified by Rayleigh staining.LPS was used to stimulate the degranulation of neutrophils to extract the supernatant of neutrophils.The activity of peroxidase myeloperoxidase(MPO)in the supernatant was determined by colorimetric method.After the proper stimulation time and concentration were determined,neutrophils were stimulated by LPS and treated with pravastatin sodium.The activity of MPO in the supernatant was measured,the content of NE in cell culture supernatant was detected by ELISA method,and the activity of NE was detected by colorimetric assay.Results After LPS stimulation,neutrophil degranulation increased,and the level of MPO,the content and activity of NE in culture supernatant were significantly increased.The level of MPO,the activity and content of NE in the supernatant of cell culture treated with pravastatin sodium decreased significantly(P < 0.05).Conclusions Pravastatin sodium can reduce the neutrophil degranulation and release of NE induced by LPS.