Inhibition of NF-κB/IL-33/ST2 Axis Ameliorates Acute Bronchiolitis Induced by Respiratory Syncytial Virus.

Liwen Zhang,Kaihong Xu,Liang Ma,Yu Wan,Baojin Cheng,Zhipeng Xu

doi:10.1155/2021/6625551

Abstract

Background/Aim Bronchiolitis is a common acute lower respiratory tract infectious disease in infants. Respiratory syncytial virus (RSV) infection is one of the main causes. Bronchiolitis can lead to a significant increase in the incidence of asthma in young children, but the mechanism of bronchiolitis transforming into asthma is still unclear. The study was aimed at investigating the role of NF-κB/IL-33/ST2 axis on RSV-induced acute bronchiolitis. Methods A total of 40 infants diagnosed with acute bronchiolitis infected by RSV, and 20 normal infants were included in this study. BALB/c mice (6-8 weeks old, 20 ± 1.1 g) were used as study models. Enzyme-linked immunosorbent assay (ELISA), quantitative real time PCR, western blot analysis, immunohistochemical staining, and flow cytometry analysis were performed to examine relevant indicators. Results IL-33 level was significantly elevated, and Th1/Th2 ratio is imbalance after in infants with acute bronchiolitis. In vivo study, we found that NF-κB/IL-33/ST2 axis is mediated the Th2 cytokine levels and BAL cell number induced by RSV. Acute bronchiolitis induced by RSV in a mouse model is attenuated after inhibition of NF-κB/IL-33/ST2 pathway. Moreover, we also confirmed that macrophages are important sources of IL-33 and are regulated by NF-κB pathway in RSV-induced mice. Conclusion We confirmed that inhibition of NF-κB/IL-33/ST2 axis could attenuate acute bronchiolitis by RSV infected. Our findings not only demonstrate the potential role of IL-33 antibody in attenuating RSV-induced lung damage but also provide a new insight into better prevention of RSV-induced asthma by mediating NF-κB/IL-33/ST2 axis.

Highlights

Asthma is a respiratory disease involving a variety of inflammatory mediators and cytokines, which has been a serious threat to human health [1]
If effective treatment measures are not taken in time, children with acute bronchiolitis may suffer from repeated wheezing and develop asthma in the future, which seriously affects pulmonary function and brings heavy mental and economic burden to their families and society [23]
In the process of airway inflammation induced by Respiratory syncytial virus (RSV), IL-33 and its specific receptor of Suppression of tumorigenesis 2 (ST2) increased significantly [24]

Summary

Introduction

Asthma is a respiratory disease involving a variety of inflammatory mediators and cytokines, which has been a serious threat to human health [1]. Previous reports showed that RSV infection accounts for 80-85% and 75-80% of asthma cases in children and adults, respectively [6, 7]. Another important reason RSV can induce asthma is that it can activate T helper 2 (Th2) cell-related cytokines such as IL-4, IL-5, and IL-10 and break the body’s immune balance [8, 9]. Recent studies have found that the treatment of cytokines secreted by Th2 cells can effectively alleviate the symptoms of acute asthma attack, while the reduction of cytokines secreted by Th1 cells does not significantly alleviate the symptoms of asthma [8, 10]. Our results suggested that IL-33, ST2, and NF-κB can serve as therapeutic targets in the treatment of RSV infected asthma

Materials and Methods

Results

Discussion

Conflicts of Interest