Abstract
Background
Neutrophilic asthma (NA) was a subtype of asthma. Soluble advanced glycosylation receptor (sRAGE) was considered to be associated with the neutrophilic airway. However, the role of sRAGE in NA still limited.
Methods
A NA mouse model was established and the levels of sRAGE in the bronchoalveolar lavage fluid (BALF) were measured by ELISA. Hematoxylin-eosin (HE) and Masson trichrome staining were used to identifying airway remodeling. Adeno-associated virus 9 (AAV9) overexpressed sRAGE and inhibitors for HMGB1, RAGE, and PI3K were used to intervene NA mouse model via tail-vein injection and intraperitoneally injection. Expressions of airway remodeling, EMT, and signaling markers were detected using qRT-PCR or western blotting. The levels of IL-17 and IL-6 in BALF were measured by ELISA. HMGB1 was applied to induce EMT of human bronchial epithelial cells (16HBE), then E-cadherin and vimentin expressions were examined after sRAGE, RAGE inhibitor, and PI3K inhibitor administration.
Results
sRAGE levels were significantly reduced in BALF and the airway remodeling was observed in the NA mouse model. AAV9-sRAGE significantly inhibited the neutrophilic airway inflammation, airway remodeling, and the expression of IL-17, IL-6, TGF-β1, RAGE, PI3K, and EMT markers -E-cadherin and vimentin in vivo. HMGB1 inhibitor, RAGE inhibitor, and PI3K inhibitor upregulated E-cadherin level. Moreover, HMGB1 promoted the EMT process via RAGE/PI3K in 16HBE cells and sRAGE reversed HMGB1- induced EMT in vitro.
Conclusion
sRAGE levels decrease in the mouse model with NA. sRAGE treatment attenuates neutrophilic airway inflammation, airway remodeling, and EMT. This suggests sRAGE may yield benefits in the treatment of NA.
Effects of microRNA-19b on airway remodeling, airway inflammation and degree of oxidative stress by targeting TSLP through the Stat3 signaling pathway in a mouse model of asthma
