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- Title
Interleukin-17A is involved in development of spontaneous pulmonary emphysema caused by Toll-like receptor 4 mutation.
- Authors
Wang, Qing-qing; Yang, Hong-zhen; Liu, Han-zhi; Mi, Su; Zhang, Xiao-wei; Yan, Hui-min; Ma, Yong-gang; Wang, Xiao-xing; Hu, Zhuo-wei
- Abstract
Aim:To explore the pathogenic role of Th17 cells and interleukin-17A (IL-17A)-associated signaling pathways in spontaneous pulmonary emphysema induced by a Toll-like receptor 4 mutant (TLR4mut).Methods:Lungs were obtained from wild-type (WT) or TLR4mut mice that were treated with or without recombinant mouse IL-17A (1 μg·kg−1·d−1, ip) from the age of 3 weeks to 3 months. Pulmonary emphysema was determined using histology, immunochemistry, and biochemical analysis. T cell polarization was determined with flow cytometry, the levels of cytokines were measured using ELISA, and the levels of IL-17A-associated signaling molecules were detected using Western blot.Results:Compared to WT mice, 3 month-old TLR4mut mice were characterized by significantly reduced infiltration of Th17 cells into lungs (2.49%±1.13 % νs 5.26%±1.39%), and significantly reduced expression levels of IL-17A (3.66±0.99 pg/μg νs 10.67±1.65 pg/μg), IL-23 (12.43±1.28 pg/μg νs 28.71±2.57 pg/μg) and IL-6 (51.82±5.45 pg/μg νs 92.73±10.91 pg/μg) in bronchoalveolar lavage fluid. In addition, p38 MAPK phosphorylation and AP-1 expression were decreased to 27%±9% and 51%±8%, respectively, of that in WT mice. Treatment of TLR4mut mice with IL-17A increased the infiltration of Th17 cells into lungs and expression levels of IL-17A, IL-6, and IL-23 in bronchoalveolar lavage fluid, attenuated MDA and apoptosis, and improved emphysema accompanied with increased phosphorylation of p38 MAPK and expression of AP-1.Conclusion:Th17 cells, in particular the cytokine IL-17A, play a crucial role in the pathogenesis of TLR4mut-induced spontaneous pulmonary emphysema. Both of them are potential targets for therapeutic strategies for pulmonary emphysema.
- Subjects
INTERLEUKINS; PULMONARY emphysema; CELL receptors; GENETIC mutation; T cells; FLOW cytometry; ENZYME-linked immunosorbent assay; LABORATORY mice
- Publication
Acta Pharmacologica Sinica, 2011, Vol 32, Issue 8, p1045
- ISSN
1671-4083
- Publication type
Article
- DOI
10.1038/aps.2011.67