Involvement of Transforming Growth Factor-[beta]-Associated Kinase 1 in Fixed Airway Obstruction in Asthmatic Patients with Longer Disease Duration Independent on Airway Eosinophilia

• Published in: Journal of asthma and allergy 2023-04, Vol.16, p.343
• Main Authors: Maneechotesuwan, Kittipong, Wongsurakiat, Phunsup, Assawabhumi, Jirawat, Kasetsinsombat, Kanda, Wongkajornsilp, Adisak
• Format: Article
• Language: English
• Subjects: Airway obstruction (Medicine); Asthma; Bone morphogenetic proteins; Comparative analysis; Enzyme-linked immunosorbent assay; Eosinophilia; Transforming growth factors
• ISSN: 1178-6965; 1178-6965
• DOI: 10.2147/JAA.S403645

Objective: Transforming growth factor-[beta]-associated kinase 1 (TAK1) mediates non-canonical TGF-[beta] signalling by promoting adhesive, migratory, proliferative and contractile responses of fibroblasts to TGF-[[beta].sub.1]. However, TAK1 expression status in asthmatic patients with or without fixed airway obstruction (FAO) is unknown. Patients and Methods: A total of 60 adult asthmatics with FAO were recruited and compared to 43 those without FAO (nFAO). TGF-[[beta].sub.1] concentrations, and total TAK1 and phosphorylated TAK1 (p-TAK1) levels were determined in sputum supernatants, cytospin, and whole cell lysate by ELISA, immunocytochemistry, and Western blot analysis, respectively, in asthmatics with and without FAO. Results: Asthmatic patients with FAO had much greater sputum TGF-[[beta].sub.1] concentrations than those without FAO. This was independent of airway eosinophilia as there was no significant difference in TGF-[[beta].sub.1] levels between high and low eosinophil counts within FAO and nFAO groups. In contrast, patients with FAO in the presence of sputum eosinophilia had greater expression of TAK1 and p-TAK1 than those without sputum eosinophilia (P=0.0032 and P=0.0061, respectively). The Western Blot data of total TAK1 and p-TAK1 were consistent with the immunocytochemistry, showing upregulation in all sputum cell types (neutrophils, eosinophils, macrophages, lymphocytes and airway epithelial cells). In addition, total TAK1 expression negatively correlated with pre- and postbronchodilator [FEV.sub.1]/FVC ratio. Conclusion: TAK1 may play a key role in asthmatic patients with fixed airway obstruction, which was independent of eosinophilic airway inflammation. The interruption of TAK1 might have favourable clinical impact. Keywords: transforming growth factor-[beta]-associated kinase 1, fixed airway obstruction, asthma