Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8

Emily DiMango, Heather J. Zar, Ruth Bryan, Alice Prince

Research output: Contribution to journalArticle

364 Scopus citations

Abstract

Respiratory epithelial cells play a crucial role in the inflammatory response during Pseudomonas aeruginosa infection in the lungs of patients with cystic fibrosis. In this study, we determined whether the binding of specific Pseudomonas gene products (pilin, flagellin) to their receptors on respiratory epithelial cells would result in production of the neutrophil chemoattractant IL-8. Pillared wild-type organisms, purified pili, or antibody to the pilin receptor (asialoGM1) evoked significant production of IL-8 by immortalized airway epithelial cells, whereas nonpiliated organisms were less able to bind to respiratory epithelial cells and stimulated much less IL-8 secretion (P < 0.01). A piliated, nonflagellated strain was also associated with decreased binding and a diminished level of IL-8 production when compared to wild-type organisms. Isogenic, nonadherent rpoN mutants, lacking pilin and flagellin, did not bind or elicit an IL-8 response. In addition, the IL-8 response was four-fold higher in a cystic fibrosis cell line compared with its corrected cell line. The Pseudomonas autoinducer, an exoproduct secreted during chronic infection, was found to stimulate IL-8 in a dose-dependent manner. P. aeruginosa adhesins, which are necessary for initial infection, directly stimulate IL-8 production by respiratory epithelial cells and therefore play a major role in the pathogenesis of Pseudomonas infection in patients with cystic fibrosis. The inflammatory response is subsequently perpetuated by Pseudomonas autoinducer which is secreted during chronic infection.

Original languageEnglish (US)
Pages (from-to)2204-2210
Number of pages7
JournalJournal of Clinical Investigation
Volume96
Issue number5
DOIs
StatePublished - Nov 1995

Keywords

  • Pseudomonas aeruginosa
  • adherence
  • autoinducer
  • interleukin-8
  • pilin

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Diverse Pseudomonas aeruginosa gene products stimulate respiratory epithelial cells to produce interleukin-8'. Together they form a unique fingerprint.

  • Cite this