Prolonged inflammatory resolution in allergic asthma relates to dysfunctional interactions between neutrophils and airway epithelium

Background: Allergic asthma is a heterogeneous disorder involving chronic airway inflammation, reversible air -flow limitation, and tissue remodeling, causing chronic airflow limitation. Most of the asthma research has been focused on elucidating the proinflammatory pathways underlying disease pathogenesis. Paradoxically, the necessity of appropriate termination and resolution of inflammation has not been recognized until recently. The latter has led to the concept of chronic inflammation developing as a result of lack of specific stop signals for the inflammatory process.Objective: To investigate the interaction between neutrophils and airway epithelium during inflammatory resolution in patients with allergic asthma.Methods: An in vitro scratch assay with cultured epithelial cells, based on live-imaging microscopy, was used to evaluate regeneration and the influence of neutrophils on resolution. Epithelial cells and autologous neutrophils were derived from healthy donors and patients with allergic asthma. Supernatants and cells were collected for enzyme-linked immunosorbent assay and transcriptional analyses at the end of the experiment.Results: Healthy epithelial cells regenerated faster than epithelial cells from patients with allergic asthma. Autologous neutrophils improved the regeneration of healthy epithelial cells but not asthmatic epithelial cells. Inter-leukin (IL)-8 and b-catenin were down-regulated in healthy epithelial cells after resolution, but not in allergic asthmatic epithelial cells.Conclusion: The prolonged duration of inflammation in the respiratory tract in patients with allergic asthma could be due to the impaired healing pattern of epithelial cells and their compromised interactions with the neutrophils.& COPY; 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Automated summary

This study investigated the interaction between neutrophils and airway epithelium during inflammatory resolution in patients with allergic asthma. The results showed that healthy epithelial cells regenerated faster than asthmatic epithelial cells, and autologous neutrophils improved the regeneration of healthy epithelial cells but not asthmatic epithelial cells. Furthermore, the expression of IL-8 and β-catenin was down-regulated in healthy epithelial cells after resolution, but not in asthmatic epithelial cells.