Nebulized Inhalation of Bacillus Calmette-Guerin Polysaccharide Nucleic Acid Attenuates Airway Hyperresponsiveness in...

Bacillus Calmette-Guerin polysaccharide nucleic acid (BCGPSN) has potential efficacy in asthma. We aim to investigate the mechanisms by which BCG-PSN attenuates asthma.

Ovalbumin (OVA) was used to establish asthma mouse models and simulate asthma injury in BEAS-2B cells. After BCG-PSN nebulization and Notch3 overexpression, acetylcholine provocation tests and immunoblotting were used to assess airway hyperresponsiveness (AHR) in mice. Hematoxylin and eosin staining was used to evaluate bronchial pathology in mice. The Mucin 5AC (MUC5AC) expression was analyzed through mRNA quantification. The Notch3/Nuclear Factor- Kappa B (NF-κB) signaling pathway in mouse lung tissues and BEAS-2B cells was analyzed by immunoblotting. The morphology and cell viability of BEAS-2B cells were examined through morphological analysis and CCK-8 assay.

OVA-induced mice showed increased AHR, a thickened bronchial basement membrane, goblet cell hyperplasia, inflammatory infiltration, and elevated lung MUC5AC. Nebulized inhalation of BCG-PSN reduced AHR and the level of MUC5AC in the lung tissues of asthmatic mice. In vivo and in vitro experiments showed that BCG-PSN treatment partially reversed the effects induced by OVA, leading to restored cell morphology, increased cell viability, and decreased expression levels of Notch3, pp65Ser276/ p65, and MUC5AC. However, overexpression of Notch3 partially counteracted the action of BCG-PSN.

The findings suggest that the Notch3/NF-κB pathway plays a key role in OVA-induced airway epithelial injury and MUC5AC overexpression. BCG-PSN appears to exert its protective effects by modulating this signaling axis.

BCG-PSN inhalation alleviates asthma-related AHR primarily by downregulating MUC5AC via the Notch3/NF-κB pathway.