Activation of STAT3 in the COPD airway epithelium.
(2026) ERJ Open Research — Vol. 12, n° 2 (2026)
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- Authors
Higham, Andrew 
- Abstract
- The mechanisms driving epithelial pathology in COPD are steadily being unveiled, confirming a role for inflammation in the disease. This study explored the interleukin (IL)-6/STAT3 axis, previously reported to link inflammation and epithelial-to-mesenchymal transition, two features of COPD at the airway epithelium level. Bronchoalveolar lavage fluid (BALF) and surgical lung tissue were obtained from nonsmoker controls, smokers and COPD patients. The activation of STAT3 and IL-6 levels were measured in these samples. Primary air-liquid interface (ALI) cultures were carried out from nonsmokers, smokers and COPD patients, and IL-6 release and mRNA levels were assessed. BEAS-2B cell cultures were exposed to sputum supernatants from COPD patients nonsmokers, with and without a pan-gp130 blocking monoclonal antibody. Finally, primary ALI cultures from nonsmokers were exposed to IL-6 vehicle and assessed for epithelial-to-mesenchymal transition and cell differentiation. IL-6 and Tyr705-phospho-STAT3 levels were increased in samples from COPD patients compared to controls, both in BALF and in the airway epithelium, as well as in ALI cultures. BEAS-2B cells exposed to COPD sputum supernatants displayed STAT3 activation that was inhibited by the pan-gp130 blocking monoclonal antibody. In addition, stimulation of ALI cultures with IL-6 induced increased vimentin expression and fibronectin release and reduced the expression of apical junctional complexes proteins, indicating epithelial-to-mesenchymal transition. Finally, no impact on airway cell differentiation was observed. The IL-6/STAT3 axis is activated in the COPD airway epithelium, presumably contributing to epithelial-to-mesenchymal transition.
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Citations
Southworth, T., Pilette, C., Mulvanny, A., Higham, A., Saputra, P. A., Belhaj, A., Lecocq, M., Detry, B., Plante-Bordeneuve, T., Singh, D., & Carlier, F. (2026). Activation of STAT3 in the COPD airway epithelium. ERJ Open Research, 12(2). https://doi.org/10.1183/23120541.00497-2025 (Original work published 2026)