Xiaoqin Li, Yuxia Cui
α7nAChR expression is reduced in asthmatic lung tissue. The α7nAChR agonist PNU-282987 attenuates airway inflammation and is associated with reduced JAK2 and STAT3 total protein expression, suggesting a potential association between α7nAChR activation and reduced JAK2/STAT3 protein expression. α7nAChR may represent a potential novel therapeutic target for asthma.
OBJECTIVE: This study investigated α7 nicotinic acetylcholine receptor (α7nAChR) expression and its relationship with the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in allergic asthma, and evaluated the therapeutic efficacy of the α7nAChR agonist PNU-282987 compared with ipratropium bromide.
METHODS: Twenty-eight BALB/c mice were randomized into four groups (n = 7 each): control (Group A), asthma (Group B), asthma + PNU-282987 (Group C), and asthma + ipratropium bromide (Group D). Asthma was induced by intraperitoneal ovalbumin sensitization (days 1,7,14) followed by nebulized 5% ovalbumin challenge (days 21,28). Groups C and D received PNU-282987 (0.5 mg/kg IP) and nebulized ipratropium bromide (0.25 mg/mL, 10 min), respectively, 2 hours post-challenge. Controls received saline. Behavioral assessment, histopathology, and ELISA for IL-4, IL-5, and IL-17 were performed. α7nAChR, JAK2, and STAT3 expression were measured by Western blot.
RESULTS: Asthmatic mice (Group B) showed significant behavioral changes, peribronchial inflammation, and airway secretions, and elevated IL-4, IL-5, and IL-17 versus controls (P < 0.05). α7nAChR was lower in Group B versus Groups A and C (P < 0.05); JAK2 and STAT3 were higher in Group B versus Groups A and C (P < 0.05). PNU-282987 (Group C) attenuated inflammation, reduced cytokines to control levels (P > 0.05), restored α7nAChR, and downregulated JAK2 and STAT3 total protein expression. Ipratropium bromide (Group D) reduced cytokines and inflammation but did not alter α7nAChR, JAK2, or STAT3 expression versus the asthma group (P > 0.05).
CONCLUSIONS: α7nAChR expression is reduced in asthmatic lung tissue. The α7nAChR agonist PNU-282987 attenuates airway inflammation and is associated with reduced JAK2 and STAT3 total protein expression, suggesting a potential association between α7nAChR activation and reduced JAK2/STAT3 protein expression. α7nAChR may represent a potential novel therapeutic target for asthma.