Induction Of Neutrophil Apoptosis By Bcl-2 Inhibitor Reduces PM Induced Airway Inflammation

In recent years,due to the industrial development and the progress of urbanization,environmental pollution is more and more serious,more and more domestic and foreign researches showed that the suspended particulate matter in the air played an important role in the rise of respiratory diseases,cardiovascular disease and lung cancer PM mainly includes industrial production emissions,soil dust in natural sources,motor vehicle exhaust or biofuel and fossil fuel combustion,PM can be deposited in the airway or directly into the alveoli,can cause many lung diseases or increase the original breathing Systemic disease.When the PM particle size is smaller,its surface area is larger and the particle settling speed is slower and the propagation distance will be farther,and can carry more toxic and harmful substances,the greater the harm to human health.The study found that exposure to a certain PM confused environment can induce significant airway hyperresponsiveness,but also induced neutrophil-based airway inflammation;can increase asthma airway inflammation,especially neutrophil Road inflammation,leading to asthma patients with reduced sensitivity to hormone therapy,but also by increasing the level of oxidative stress in the cells to induce airway epithelial transformation,but also make asthma patients more prone to airway remodeling.There are many studies that will induce inflammatory cell death and remove infiltrated inflammatory cells as an important treatment for the treatment of inflammatory diseases.Moreover,studies have shown that inhibitor of apoptosis inhibitor Bcl-2 can be more effective in the treatment of respiratory airway inflammation,such as asthma,especially neutrophils for hormone therapy,by inducing apoptosis of eosinophils or neutrophils Cellular asthma.In this study,we investigated the relationship between PM-induced airway inflammation and the expression of Bcl-2,and whether the inhibitor of apoptosis inhibitor Bcl-2 could be alleviated on PM induces airway inflammation to develop new strategies for the new treatment of PM-induced airway inflammation.Objective:Established the model of PM-induced airway inflammation in mice and to study the role of Bcl-2 in PM-induced airway inflammation and to investigate whether apoptosis protein is involved in PM-induced by Bcl-2 overexpression of mice Airway inflammation play an important role.Methods:The WT mice were instillated with standard PM.The airway inflammation model was established.Flow cytometry was used to detect the apoptosis of inflammatory cells with Annexi V/PI,to detect whether PM-induced airway inflammation and inflammatory cells Death related.The expression of Bcl-2 protein in alveolar lavage fluid after PM intervention was also detected.The apoptosis of inflammatory cells was correlated with Bcl-2.The effect of Bcl-2 on PM-induced airway inflammation was then increased by airway infusion of PM in Vav-Bcl-2 transgenic mice.Finally,the mice treated with Bcl-2 selective inhibitor ABT199 were treated with PM to see if it was possible to relieve PM airway inflammation caused by PM and to detect apoptosis of inflammatory cells using Annexi V/PI to determine whether ABT199 increased inflammation through Cell apoptosis and thus alleviate PM-induced airway inflammation.Results:The total number of alveolar lavage fluid in the alveolar lavage fluid increased significantly,and the results showed that PM could significantly increase the aggregation of inflammatory cells.Annexi V/PI assay showed that the apoptosis of inflammatory cells in PM was significantly higher than that in NS group.And IF and flow detection results also showed that BALF cells Bcl-2 expression also increased significantly.Compared with WT mice,the expression of neutrophils,the aggregation of airway inflammation and the expression of neutrophil chemokines were significantly increased in the Bcl-2 overexpression mice compared with WT mice after PM airway infusion and the time of self degree is slowing down.Bcl-2 selective inhibitor after the last infusion of PM showed that Bcl-2 inhibitor could significantly induce neutrophil apoptosis and reduce PM-induced airway inflammation.Conclusion:PM induced the increase of total cell and neutrophil cell in BALF.The inflammation induced by PM in vav-Bcl-2 mice is more serious than WT mice.vav-Bcl-2 mice delayed resolution of PM induced airway inflammation.Delayed clearance of airway inflammatory cells in vav-Bcl-2 transgenic mice.Bcl-2 Inhibitor Reduces PM induced airway inflammation,inhibition of Bcl-2 induces apoptosis of neutrophil from PM induced airway inflammation.