Alpha7 nicotinic acetylcholine receptor activation attenuates allergic airway inflammation and is associated with heme oxygenase-1 induction.

Abstract

BACKGROUND: Activation of the α7 nicotinic acetylcholine receptor (α7nAChR) exerts anti-inflammatory effects; however, its role in allergic airway inflammation remains poorly understood. This study investigated how GTS-21 treatment, consistent with α7nAChR activation, influences airway inflammation and epithelial cytokine responses. METHODS: A murine model of allergic airway inflammation was established in female C57BL/6J mice by repeated house dust mite (HDM) exposure. Mice received intratracheal GTS-21 or phosphate-buffered saline (PBS) prior to each HDM challenge. Airway inflammation and cytokine levels were then evaluated., BEAS-2B human airway epithelial cells were treated with GTS-21 or PBS, followed by stimulation with HDM and lipopolysaccharide (LPS). Thymic stromal lymphopoietin (TSLP) production was quantified, and RNA sequencing was performed to analyze gene expression changes. RESULTS: Intratracheal GTS-21 administration significantly attenuated HDM-induced eosinophilic airway inflammation in mice and reduced TSLP and type 2 cytokine levels. In BEAS-2B cells, GTS-21 treatment similarly suppressed LPS- and HDM-induced TSLP production. RNA sequencing revealed that GTS-21 treatment upregulated heme oxygenase-1 (HO-1) expression. Increased HO-1 expression was associated with reduced TSLP production under these experimental conditions. CONCLUSION: GTS-21 attenuated allergic airway inflammation and suppressed epithelial TSLP production in association with increased HO-1 expression. These findings suggest that cholinergic receptor-associated signaling may modulate epithelial inflammatory responses in allergic airway inflammation.