Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
Copyright 2016, American College of Chest Physicians. All Rights Reserved.
SESSION TITLE: COPD II
SESSION TYPE: Original Investigation Poster
PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM
PURPOSE: Recent studies suggest that has been implicated in the pathogenesis of various inflammatory diseases. It is currently unknown, however, whether YKL-40 plays a role in COPD airway remodeling.
METHODS: Here, we evaluated IL-17A expression in the lung of patients with COPD and smokers without COPD, as well as in controls. The association between IL-17A expression and airway remodeling was analyzed. In parallel, IL-17A-/- mice and wild-type control animals were exposed to cigarette smoke for 3 months, and airway inflammation and airway remodeling were assessed. The effects of IL-17A on collagen synthesis of primary human lung fibroblasts were also evaluated.
RESULTS: Our data showed that IL-17A expression were elevated in the lung of COPD patients as compared to smokers without COPD and non-smokers. IL-17A expression correlated positively with collagen deposition. After exposing wild-type and IL-17A-/- mice to mainstream cigarette smoke (CS) for 3 months, IL-17A expression was increased in mice upon CS exposure. CS-treated IL-17A-/- mice exhibited reduced lung collagen content, smooth muscle area, mucus-producing cells, and inflammatory cell accumulation as compared with wild-type mice. Reduced matrix metalloproteinase-2 activity and expression of transforming growth factor-β1 and vascular endothelial growth factor were observed in CS-treated IL-17A-/- mice. Lung fibroblasts from IL-17A-/- mice showed reduced proliferation, migration, collagen deposition, and α-smooth muscle actin expression in comparison with CS-treated wild-type lung fibroblasts. Stimulation with IL-17A promoted collagen production in lung fibroblasts through ERK- and p38-dependent mechanisms.
CONCLUSIONS: we demonstrate that IL-17A is key for the development of CS-induced airway remodeling in COPD. In response to allergen, IL-17A induces the switching of lung fibroblasts to a pro-fibrogenic myofibroblast phenotype. The current data may provide insight into the underlying pathogenesis of COPD, in which IL-17A has an important pathogenic role.
CLINICAL IMPLICATIONS: IL-17A play an improtant in airway inflammation and airway remodeling. Thus, therapeutics targeting IL-17A might prove efficacious in the treatment of COPD.
DISCLOSURE: The following authors have nothing to disclose: Tianwen Lai, Bao-ping Tian, Chao Zhang, Yue Hu, Luanqing Che, Feng Xu, Songmin Ying, Wen Li, Zhihua Chen, Huahao Shen
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