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

Overview

MeSH

  • Base Sequence
  • Bronchoalveolar Lavage Fluid
  • Cell Line
  • Chemotaxis, Leukocyte
  • Epithelium
  • Gene Expression
  • Humans
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction
  • RNA, Messenger

MeSH Major

  • Bronchi
  • Cystic Fibrosis
  • Interleukin-8
  • Neutrophils
  • Pancreatic Elastase

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.

publication date

  • May 1992

has subject area

  • Base Sequence
  • Bronchi
  • Bronchoalveolar Lavage Fluid
  • Cell Line
  • Chemotaxis, Leukocyte
  • Cystic Fibrosis
  • Epithelium
  • Gene Expression
  • Humans
  • Interleukin-8
  • Molecular Sequence Data
  • Neutrophils
  • Oligodeoxyribonucleotides
  • Pancreatic Elastase
  • Polymerase Chain Reaction
  • RNA, Messenger

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC443018

Digital Object Identifier (DOI)

  • 10.1172/JCI115738

PubMed ID

  • 1569186

Additional Document Info

start page

  • 1478

end page

  • 1484

volume

  • 89

number

  • 5