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

Hidenori Nakamura, Kunihiko Yoshimura, Noel G. McElvaney, Ronald Crystal

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1478-1484
Number of pages7
JournalJournal of Clinical Investigation
Volume89
Issue number5
DOIs
Publication statusPublished - 1 Jan 1992
Externally publishedYes

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Keywords

  • Airway inflammation
  • Anti-serine pro-tease
  • Bronchial epithelium
  • Cytokine
  • Neutrophil chemoattractant

ASJC Scopus subject areas

  • Medicine(all)

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