Raised interleukin-17 is immunolocalised to neutrophils in cystic fibrosis lung disease.
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-neutrophilic mediators by CF epithelial cells, suggesting potential for a positive feedback element in airway inflammation.
Applied Immunobiology and Transplantation Group, Institute of Cellular Medicine, Newcastle University, and Department of Cardiopulmonary Transplantation, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Sir William Leech Centre For Lung Research, Freeman Hospital, Newcastle Upon Tyne, NE7 7DN, UK. m.j.brodlie@ncl.ac.uk
M
M
Brodlie
M C
MC
McKean
G E
GE
Johnson
A E
AE
Anderson
C M U
CM
Hilkens
A J
AJ
Fisher
P A
PA
Corris
J L
JL
Lordan
C
C
Ward
D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016040:Lung Transplantation; D009504:Neutrophils / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D013183:Sputum / Q000382:microbiology
D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D016178:Granulocyte-Macrophage Colony-Stimulating Factor