IL-25Secreted From Epithelial Cells Has The Potential To Promote Airway Remodeling In Asthma

BACKGROUND:Bronchial asthma is a chronic inflammatory disease that is involved by eosinophils (EOS), mast cells, T lymphocytes and other inflammatory cells and cellular components, and usually the structure changes of the airway epithelium are the main pathological features. The three major pathological changes in asthma are: airway inflammation, airway remodeling and smooth muscle dysfunction. Airway remodeling is the main feature of bronchial asthma, its main pathological changes are: changes in epithelium function and structure; basement membrane thickness; microvascular reconstruction; smooth muscle hyperplasia and hypertrophy; mucous glands and goblet cells hyperplasia. Of all above, the core feature is the function and structure changes of the epithelium. Airway remodeling is the pathological basis of the lung function impairment, which can lead to the labor loss, the social and medical burden increasing. EOS and airway inflammation are closely related, but there is much controversy with the relationship between EOS and airway remodeling. Interleukin25(also known as IL-17) is one of the IL-17family numbers reported by Fort first that is a cytokine secreted by activated Th2cells and plays an important role in the starting, promoting and regulation of the Th2type immune response. Previous study found that the epithelium damage could increase the release of IL-25, and thus play a pivotal role in airway inflammation and airway hyperresponsiveness. But there was no report about the relationship between IL-25and airway remodeling. OBJECTIVE:To explore the function and significance of IL-25in the pathogenesis of eosinophilic asthma (EA) and non-eosinophilic asthma (NEA) by examining its expression in serum, induced sputum and bronchial epithelial mucosal of asthmatic patients.METHODS:We enrolled55untreated asthmatic patients and27healthy controls. The level of IL-25in serum and induced sputum was determined by ELISA. The expression of IL-25in bronchial epithelium was quantified by immunohistochemistry. Hematoxylin and eosin (H&E) staining revealed the morphological changes in epithelia.RESULTS:Initial patients’conditionsFive patients with asthma and two control subjects dropped out because they could not tolerate sputum induction. Therefore, we analyzed data for50asthmatic patients and25controls. The EA and NEA groups did not differ in number, age, sex or respiratory function, which did differ from the respiratory function of control subjects.EosinophiliaBecause the threshold identifying EA and NEA was somewhat arbitrary, we used a cut-off proportion of3%eosinophils in induced sputum to distinguish eosinophilic and non-eosinophilic airway inflammation in patients with asthma. The EA group showed substantial eosinophils, with few in the NEA and control groups. The NEA group showed increased number of lymphocytes. However, EA and NEA groups did not differ in other pathological or clinical features.Serum and induced sputum levels of IL-25As compared with healthy control subjects, both groups of asthmatic patients showed increased levels of IL-25in peripheral blood serum and induced sputum, with no significant difference between the EA and NEA groups (p>0.05).Airway epithelium levels of IL-25Positive staining of IL-25was evident in airway epithelial cells of EA and NEA patients as compared with control subjects. Examples of the expression of IL-25in a patient of EA, a patient of NEA and a control subject are illustrated in Figure3.Basement membrane thicknessRepresentative biopsies for basement membrane thickness analysis in EA and NEA are in Figure4. Median (range) reticular basement membrane was thicker for both EA and NEA patients than controls (median, range:5.32,[2.55-10.51] μm and5.12,[2.72-9.28] μm vs.2.50,[1.02-4.44] μm; p<0.0001for both).Correlational of IL-25level and basement membrane thicknessMean basement membrane thickness was positively correlated with serum IL-25level for EA patients (r=0.880, p<0.01) and NEA patients (r=0.978, p<0.01). Simultaneously, mean basement membrane thickness was positively correlated with sputum IL-25level for both groups (r=0.894, p<0.01; r=0.984, p<0.01, respectively).CONCLUSION:IL-25secreted from epithelial cells may promote airway remodeling in asthma. IL-25level was increased both in peripheral blood and bronchial epithelium. Moreover, basement membrane thickness was independent of eosinophil amount, which may not be necessary for airway remodeling in asthma.