Targeting the CEACAM6-ELANE axis to regulate the PI3K/AKT/NF-?B signaling pathway: a new strategy to improve neutrophilic airway inflammation in juvenile asthma.

Abstract

Background: Neutrophil-infiltrating inflammation is closely linked to severe asthma in teenagers, and its mechanism needs to be investigated. CEACAM6 is a critical molecule that regulates neutrophil function and is significantly expressed in the airways of asthmatic patients, but its precise role in the disease and downstream signaling mechanisms remain unknown. The goal of this study was to investigate the role and mechanism of CEACAM6 in neutrophil airway inflammation.

Methods: The GSE188424 data set was analyzed using bioinformatics. An OVA-induced juvenile asthma mouse model was created utilizing CEACAM6 gene knockout mice. CEACAM6 was knocked down in BEAS-2B cells using siRNA, and LPS was utilized to produce inflammation. Molecular and phenotypic studies were carried out using Western blot, Co-IP, ELISA, and flow cytometry.

Results: CEACAM6 expression in asthmatic lung tissue was significantly elevated. In mice, knocking down CEACAM6 drastically reduces airway neutrophil inflammation and inflammatory factor release. Cell tests demonstrated that CEACAM6 knockdown reduced LPS-induced epithelial cell damage and inflammation. CEACAM6 binds to elastase, neutrophil expressed (ELANE), activating the PI3K/AKT/NF-κB signaling cascade. ELANE supplementation reversed the anti-inflammatory effects of CEACAM6 knockdown.

Conclusion: CEACAM6 increases neutrophil airway inflammation by binding to ELANE and activating the PI3K/AKT/NF-κB pathway. Targeting the CEACAM6-ELANE axis could be a novel method for treating neutrophilic asthma.