Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line

The respiratory manifestations of cystic fibrosis (CF) are characterized by neutrophil-dominated airway inflammation. Since a variety of inflammatory stimuli are capable of inducing bronchial epithelial cells to express the gene for IL-8, a cytokine that attracts and activates neutrophils, mediators...

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Bibliographic Details
Published in:The Journal of clinical investigation 1992-05, Vol.89 (5), p.1478-1484
Main Authors: NAKAMURA, H, YOSHIMURA, K, MCELVANEY, N. G, CRYSTAL, R. G
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
Bronchi - physiopathology
Bronchoalveolar Lavage Fluid
Cell Line
Chemotaxis, Leukocyte
Cystic Fibrosis - physiopathology
Epithelium - physiology
Gene Expression
Humans
Interleukin-8 - genetics
Medical sciences
Molecular Sequence Data
Neutrophils - enzymology
Oligodeoxyribonucleotides - chemistry
Pancreatic Elastase - metabolism
Pneumology
Polymerase Chain Reaction
RNA, Messenger - genetics
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Summary:The respiratory manifestations of cystic fibrosis (CF) are characterized by neutrophil-dominated airway inflammation. Since a variety of inflammatory stimuli are capable of inducing bronchial epithelial cells to express the gene for IL-8, a cytokine that attracts and activates neutrophils, mediators in respiratory epithelial lining fluid (ELF) of CF individuals might induce IL-8 production by epithelial cells, thus recruiting neutrophils to the airways. BET-1A human bronchial epithelial cells at rest or incubated with normal ELF showed little IL-8 gene expression, but after incubation with CF ELF, a marked increase in IL-8 transcript levels was observed. CF ELF contained high levels of neutrophil elastase (NE) and various serine protease inhibitors prevented CF ELF from inducing IL-8 gene expression in BET-1A cells, suggesting that NE was the dominant inducer for IL-8 production in CF ELF. The addition of purified NE caused BET-1A cells to increase IL-8 gene transcription with accumulation of mRNA transcripts and to release IL-8-like neutrophil chemotactic activity. These observations suggest a self-perpetuating inflammatory process on the CF bronchial surface where NE released by neutrophils induced the bronchial epithelium to secrete IL-8, which in turn recruits additional neutrophils to the bronchial surface.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI115738