Sputum IL-1? Associated With Poor Lung Function Improvement And Promotes EMT Of Bronchial Epithelial Cells In Asthma Patients With Neutrophilic Phenotype

Objective: We measured IL-1? in sputum in patients with bronchial asthma,assessed the association of sputum IL-1? with lung function in patients,and verified the role of IL-1? in Epithelial-Mesenchymal Transition.Methods: We included 51 patients and 29 controls with sufficient sputum-inducing inflammatory cells to collect general data,pulmonary function test results,blood routine results,serum total Ig E results,Fe NO,asthma symptom scores,and treatment status.We also collected the patient's induced sputum,peripheral blood samples,and extracted RNA from the sputum sample.Asthma patients were followed up to understand the medication needed to maintain symptoms,and the lung function and symptom scores after treatment were collected.We collected the patient's bronchial mucosal tissue by bronchoscopy and used IPP software to measure the thickness of the patient's reticular basement membrane.A total of 28 mucosal biopsies of asthmatics were collected,and we performed immunohistochemistry on EMT-related proteins.In vitro,we performed experiments with IL-1? with/without TGF-beta/IL-4 stimulation in A549 cells to investigate the expressions of EMT markers.Results: 51 asthmatic patients,with induced sputum eosinophils 3%,neutrophils 61% as the boundary,were divided into eosinophilic asthma,neutrophilic asthma,paucigranulocytic asthma,mixed granulocytic asthma.Neutrophil asthma lung function improvement rate was poor(p<0.05).The expression of IL-1? m RNA was the highest in neutrophil asthma(p<0.05).It was also found that sputum IL-1? m RNA was negatively correlated with lung function improvement rate in neutrophil asthma(p<0.05).IL-1? in the supernatant was negatively correlated with the improvement of lung function in all 51 asthma(p<0.05).The reticular basement membrane of asthmatic patients was thicker than that of healthy controls(p<0.05).Airway epithelial immunohistochemistry in asthmatic patients showed that the expression of E-cadherin decreased and that of fibronectin increased(p<0.05).In cell experiments,IL-1? alone did not promote EMT in human alveolar type II epithelial cell lines,but IL-1? combined with TGF-?1 greatly enhanced the EMT effect of TGF-?1 on alveolar type II epithelial cell lines(p<0.05).Conclusions: In patients with neutrophilic asthma,IL-1? may be associated with poor lung function improvement.Meanwhile,IL-1? could promote TGF-?1 inducing EMT process of epithelial cells in asthma.