Dexamethasone Alleviate Airway Inflammation Of Asthma In Mice By Inhibiting The Activation Of NLRP3 Inflammasome

Background Bronchial asthma(asthma)is a common chronic airway inflammatory disease involving different types of inflammatory cells and their products.Data from the World Health Organization(WHO)show that about 300 million people worldwide suffer from asthma.The incidence of allergic asthma has continued to rise over the past few decades.However,dexamethasone(DEX)is still the main drug in the treatment of asthma.But,the mechanism of DEX resolute symptoms of asthma is not completely clear.Interestingly,a large number of studies have shown that lung epithelial cells express NLRP3 inflammasome.NLRP3 inflammasome is a widespread feature of inflammatory diseases.Researches have shown that activation of NLRP3 inflammasome can promote the cleavage of pro-Caspase-1 to active Caspase-1.Then pro-IL-1β and pro-IL-18 will cleavage into IL-1β and IL-18,so as to promote the occurrence and development of inflammation.At the same time,the study pointed out that this process may lead to a vicious circle of asthma.As an important drug in the treatment of asthma,does DEX also play an important role by affecting this process?Objectives The allergic airway inflammation model in C57 mice was established by aerosol inhalation of ovalbumin(OVA).We aimed to analyze the effect of DEX on airway inflammation in OVA-induced mice and whether this effect is related to the inhibition of the activation of NLRP3 inflammasome.Methods Female(C57BL/6)mice were used to establish the allergic airway inflammation model by inhalation OVA.The mice were randomly divided into three groups: control group,model group and experimental group.The experimental group was treated by intraperitoneal injection of 2mg/kg DEX,and the control group and model group were injected with the same amount of saline.The number of inflammatory cells in bronchi alveolar lavage fluid(BALF)was classified and counted by Swiss-Giemsa staining,and the contents of IL-1β,IL-5,IL-17 and IL-18 in BALF were detected by ELISA.The degree of inflammatory cells’ infiltration,thickness of airway wall and the proliferation of mucous cells in lung tissue were observed by H-E and PAS staining.The proteins expression of NLRP3,Pro-Caspase-1,Caspase-1,IL-1β,IL-6 and IL-17 in lung tissue was detected by Western blotting.Results Inflammatory cells’ infiltration,airway mucus secretion and goblet cell proliferation in the model group were higher than those in the normal group(P<0.05).The total and classified number(monocytes,lymphocyte,neutrophil and eosinophil)of inflammatory cells,the levels of IL-1β,IL-5,IL-17 and IL-18 were significantly increased in BALF.The activity of NLRP3 inflammasome and the protein contents of Pro-Caspase-1,Caspase-1,Capase-1/Pro-Caspase-1,IL-1β,IL-6 and IL-17 in lung tissue were also significantly increased(P<0.05).However,DEX significantly inhibited OVA-induced inflammatory cells’ infiltration,airway mucus secretion and goblet cell proliferation in asthma mice(P<0.05).After DEX treatment,the total number of inflammatory cells,the number of classified inflammatory cells and the levels of IL-1β,IL-5,IL-17 and IL-18 in the BALF of the experimental group were significantly decreased(P < 0.05)after DEX treatment.DEX also significantly inhibited the activity of NLRP3 inflammasome and reduce the protein contents of Pro-Caspase-1,Caspase-1,Capase-1/Pro-Caspase-1,IL-1β,IL-6 and IL-17 in lung tissues(P<0.05).Conclusion In conclusion,these data showed that DEX alleviated allergic airway inflammation by inhibiting the activity of NLRP3 inflammasome and the levels of IL-1β and IL-18.Our study enriched the theoretical basis of DEX in the treatment of allergic diseases such as asthma.It also provides a certain theoretical basis for the later researches.