期刊
EUROPEAN RESPIRATORY JOURNAL
卷 37, 期 6, 页码 1378-1385出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00067110
关键词
Cystic fibrosis; cytokines; interleukin-17; neutrophils; T-helper cell type 17; transplantation
资金
- Newcastle upon Tyne Hospitals NHS Foundation Trust Special Trustees
- joint Medical Research Council/CF Trust
- Medical Research Council
- MRC [G0500705, G0800419] Funding Source: UKRI
- Medical Research Council [G0500705, G0800419] Funding Source: researchfish
Interleukin (IL)-17 is pivotal in orchestrating the activity of neutrophils. Neutrophilic inflammation is the dominant pathology in cystic fibrosis (CF) lung disease. We investigated IL-17 protein expression in the lower airway in CF, its cellular immunolocalisation and the effects of IL-17 on CF primary bronchial epithelial cells. Immunohistochemistry was performed on explanted CF lungs and compared with the non-suppurative condition pulmonary hypertension (PH). Airway lavages and epithelial cultures were generated from explanted CF lungs. Immunoreactivity for IL-17 was significantly increased in the lower airway epithelium in CF (median 14.1%) compared with PH (2.95%, p=0.0001). The number of cells staining positive for IL-17 in the lower airway mucosa was also increased (64 cells.mm(-1) compared with 9 cells.mm(-1) basement membrane, p=0.0005) and included both neutrophils in addition to mononuclear cells. IL-17 was detectable in airway lavages from explanted CF lungs. Treatment of epithelial cultures with IL-17 increased production of IL-8, IL-6 and granulocyte macrophage colony-stimulating factor. In conclusion, immunoreactive IL-17 is raised in the lower airway of people with CF and localises to both neutrophils and mononuclear cells. IL-17 increases production of pro-neutrophilicmediators by CF epithelial cells, suggesting potential for a positive feedback element in airway inflammation.
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