Improvement of RSV-Induced Asthma in Mice: A Study Based on Icariin-Mediated PD-1.

Abstract

Background: Infection with respiratory syncytial virus (RSV) has the potential to exacerbate asthma by causing prolonged inflammation in the airways. Mounting evidence has revealed the significant involvement of programmed cell death protein-1 (PD-1) in the development of asthma. Although icariin (IC) has shown potential in improving airway remodeling in ovalbumin (OVA)-induced asthma, its impact and underlying mechanisms in cases of asthma aggravated by RSV infection are not thoroughly understood.

Objective: To explore the effect of IC on RSV-infected asthmatic mice and the mechanism involving PD-1.

Methods: A model of asthmatic mice infected with RSV was developed. To evaluate the effects of IC treatment, general behavioral characterization, histopathologic analysis, bronchoalveolar lavage fluid (BALF) analysis, and enzyme-linked immunosorbent assays (ELISA) were performed to assess the frequency of sneezing and nose scratching, the content of OVA-specific IgE, oxidative stress and airway inflammation in mice. Apoptosis was also assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Finally, the expression levels of apoptosis protein, oxidative stress-related protein, and PD-1 were assessed by western blot.

Results: IC significantly ameliorated the sneezing and nose-scratching frequency (p < 0.001) and decreased OVA-specific IgE levels in asthmatic mice infected with RSV (p < 0.01). IC treatment remarkably reduced the infiltration of inflammatory cells around the alveoli and lowered the overall inflammation score. It also notably decreased the levels of inflammatory cytokines interleukin-4 (IL-4), IL-13, and IL-5, and decreased the numbers of neutrophils, eosinophils, and macrophages in the bronchoalveolar lavage fluid (BALF) (p < 0.001). IC ameliorated oxidative stress in RSV-infected asthmatic mice (p < 0.001). In addition, IC reduced apoptosis while increasing PD-1 expression in asthmatic mice infected with RSV (p < 0.001). Interestingly, si-PD-1 significantly reversed IC inhibition of inflammatory cytokines and apoptosis-related proteins, and promoted PD-1 protein expression (p < 0.01). The findings suggested that IC might be effective in alleviating asthma triggered by RSV in mice by regulating the expression of PD-1.

Conclusion: IC ameliorated RSV-induced asthma in mice by regulating PD-1 expression, and may hold promise as a potential therapeutic agent for RSV-induced asthma in mice. These findings provide valuable insights into the possibility of using IC as a treatment option for asthma caused by RSV.