IL-9 exacerbates the development of chronic obstructive pulmonary disease through oxidative stress

S.-C. Zou, L.-L. Pang, Q.-S. Mao, S.-Y. Wu, Q.-F. Xiao

Department of Pneumology, Yantai Yuhuangding Hospital, Yantai, China. qf868686@sina.com

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• Respiratory Medicine

OBJECTIVE: To investigate the role of IL-9 in chronic obstructive pulmonary disease (COPD), and to explore its potential mechanism.

MATERIALS AND METHODS: A mouse COPD model was established by exposure to cigarette smoke. COPD mice were then randomly assigned into two groups, including: the PBS group and the IL-9 antibody group. The above two groups were treated with phosphate-buffered saline (PBS) or IL-9 injection, respectively. The histopathological changes in lung tissues of mice were observed by hematoxylin-eosin (H&E) staining. Immunohistochemistry was performed to detect IL-9-positive (IL-9+) cells in lung tissues. Expression levels of IL-9, sIL-9R, STAT3, and p-STAT3 in peripheral blood of mice were determined by quantitative Real time-polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot, respectively. In addition, the expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected.

RESULTS: H&E staining results showed that the airway wall structure of COPD mice in the PBS group was irregular. Ciliated columnar epithelium exhibited marked degeneration, necrosis and shedding. Besides, numerous inflammatory cell infiltration, narrowing and rupture of the alveolar septa, and larger cysts fused by adjacent alveoli were observed. H&E staining also indicated that the structure of alveolar epithelium was severely impaired in COPD mice. However, the pathological changes in lung tissues of mice in the IL-9 antibody group were much milder than those of the PBS group. Immunohistochemistry results showed a significant deposition of IL-9+ cells in the lung tissues of the PBS group. Meanwhile, the mRNA and protein levels of IL-9, sIL-9R, and p-STAT3 in the PBS group were also remarkably higher than those of the IL-9 antibody group. In addition, SOD content in the PBS group was significantly decreased, whereas the levels of MDA and ROS were significantly increased than those of the IL-9 antibody group.

CONCLUSIONS: IL-9 activated STAT3 and aggravated lung injury in COPD mice by increasing inflammatory and oxidative stress.

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