Study On The Mechanism Of IL-17 And IL-37 On Airway Inflammation In Asthma Mice

Objective:Asthma is a chronic airway inflammation.Due to the diversity of host-environment interactions and different stimuli,the pathogenesis of asthma is still complex.Existing studies show that neutrophilic asthma responds poorly to conventional treatment options and poses a threat to patient quality of life and life safety,while IL-17 has a pro-inflammatory role and IL-37 has an anti-inflammatory effect in airway inflammatory response.In this study,a mouse model of neutrophil asthma was established by using ovalbumin(OVA)combined with lipopolysaccharide(LPS).By measuring the content of IL-17 and IL-37 in BALF and lung tissue of mice,the role of IL-17 and IL-37 in the pathogenesis of neutrophil asthma mouse model were explored,providing a new way for the prevention and treatment of asthma disease.Methods:18 female Balb/C mice were randomly divided into 3 groups:control group(Con),asthma model group(OVA+LPS),dexamethasone intervention group(OVA+LPS+Dex).In the sensitization stage:The asthma model group(OVA+LPS)and dexamethasone intervention group(OVA+LPS+Dex)were given intraperitoneal injection of 0.2ml mixture(OVA20ug+aluminum hydroxide powder 4mg)and nasal drip of 0.2%OVA 50μl+LPS 1 μg on the 1st,7th,and 14th day.The control group(Con)was treated with equal volume of normal saline.Challenge stage:from 21d to 27d,the control group was given daily inhalation of normal saline,30min/day,the asthma model group(OVA+LPS)and dexamethasone intervention group(OVA+LPS+Dex)were given daily inhalation of 2%OVA,30min/day.From the 21th day to the 27th day,the control group and the asthma model group were given saline intraperitoneal injection,and the dexamethasone intervention group was injected with 0.2ml dexamethasone sodium phosphate(2ml/kg)before atomization 30min.The bronchoalveolar lavage fluid(BALF)were collected from each group within 24 hours after the end of the last stimulation.and the inflammatory cells in BALF were classified and counted.The concentrations of IL-17 and IL-37 in BALF were determined by ELISA.The lung tissues of mice were extracted,and the pathological changes of lung tissue was performed by H&E.The expressions of mRNA IL-17 and IL-37 in lung tissues were measured by real-time fluorescent quantitative PCR(qRT-PCR).Results:(1)Compared with the control group,the total number of inflammatory cells,and the number of neutrophils and eosinophils in the BALF of the asthma model group were significantly increased(P<0.01);the level of IL-17 in BALF of mice in the asthma model group was significantly increased(P<0.01),and the level of IL-37 was significantly decreased(P<0.01);airway epithelial cells were damaged in the asthma model group,showing different degrees of necrosis and exfoliation,the lung interstitial tissue was accompanied by a large amount of inflammatory cells,mainly neutrophils;real-time PCR indicated that the expression level of IL-17mRNA was significantly increased and the expression level of IL-37mRNA was significantly decreased in the lung tissues of the asthma model group,and the difference was statistically significant(P<0.01).(2)Compared with the asthma model group,the total number of inflammatory cells,and the number of neutrophils and eosinophils in the BALF of the dexamethasone group decreased significantly(P<0.01);the level of IL-17 in BALF of mice in the dexamethasone group was decreased,and the level of IL-37 was increased,and also the difference was statistically significant(P<0.05);the local airway epithelial cells of mice in the dexamethasone group were slightly exfoliated,and a small number of inflammatory cells could be infiltrated in the lung stroma,mainly neutrophils;real-time PCR indicated that the expression level of IL-17mRNA was decreased and the expression level of IL-37mRNA was increased in the lung tissues of mice in the dexamethasone group,and the difference was statistically significant(P<0.05).Conclusions:The asthma model group showed severe airway inflammation,and the IL-17 concentration in alveolar BALF and the expression of IL-17mRNA in lung tissue were increased,while the IL-37 concentration in BALF and the expression of IL-37mRNA in lung tissue were decreased.After dexamethasone intervention,airway inflammation was reduced,IL-17 concentration in BALF and IL-17mRNA expression in lung tissue decreased,IL-37 concentration in BALF and IL-37mRNA expression in lung tissue increased,suggesting that IL-17 promotes the progression of asthma,while IL-37 inhibits the progression of asthma.