Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells

Gerene M. Denning, Laura A. Wollenwebber, Michelle A. Railsback, Charles D. Cox, Lynn L. Stoll, Bradley E Britigan

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Pseudomonas aeruginosa, an opportunistic human pathogen, causes acute pneumonia in patients with hospital-acquired infections and is commonly associated with chronic lung disease in individuals with cystic fibrosis (CF). Evidence suggests that the pathophysiological effects of P. aeruginosa are mediated in part by virulence factors secreted by the bacterium. Among these factors is pyocyanin, a redox active compound that increases intracellular oxidant stress. We find that pyocyanin increases release of interleukin-8 (IL-8) by both normal and CF airway epithelial cell lines and by primary airway epithelial cells. Moreover, pyocyanin synergizes with the inflammatory cytokines tumor necrosis factor alpha and IL-1α. RNase protection assays indicate that increased IL-8 release is accompanied by increased levels of IL-8 mRNA. The antioxidant n-acetyl cysteine, general inhibitors of protein tyrosine kinases, and specific inhibitors of mitogen- activated protein kinases diminish pyocyanin-dependent increases in IL-8 release. Conversely, inhibitors of protein kinases C (PKC) and PKA have no effect. In contrast to its effects on IL-8 expression, pyocyanin inhibits cytokine-dependent expression of the monocyte/macrophage/T-cell chemokine RANTES. Increased release of IL-8, a potent neutrophil chemoattractant, in response to pyocyanin could contribute to the marked infiltration of neutrophils and subsequent neutrophil-mediated tissue damage that are observed in Pseudomonas-associated lung disease.

Original languageEnglish (US)
Pages (from-to)5777-5784
Number of pages8
JournalInfection and Immunity
Volume66
Issue number12
StatePublished - Dec 1 1998

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Pyocyanine
Pseudomonas
Interleukin-8
Epithelial Cells
Cystic Fibrosis
Pseudomonas aeruginosa
Lung Diseases
Neutrophils
Cytokines
Chemokine CCL5
Neutrophil Infiltration
Chemotactic Factors
Virulence Factors
Ribonucleases
Cross Infection
Mitogen-Activated Protein Kinases
Interleukin-1
Chemokines
Oxidants
Protein-Tyrosine Kinases

ASJC Scopus subject areas

  • Immunology

Cite this

Denning, G. M., Wollenwebber, L. A., Railsback, M. A., Cox, C. D., Stoll, L. L., & Britigan, B. E. (1998). Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells. Infection and Immunity, 66(12), 5777-5784.

Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells. / Denning, Gerene M.; Wollenwebber, Laura A.; Railsback, Michelle A.; Cox, Charles D.; Stoll, Lynn L.; Britigan, Bradley E.

In: Infection and Immunity, Vol. 66, No. 12, 01.12.1998, p. 5777-5784.

Research output: Contribution to journalArticle

Denning, GM, Wollenwebber, LA, Railsback, MA, Cox, CD, Stoll, LL & Britigan, BE 1998, 'Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells', Infection and Immunity, vol. 66, no. 12, pp. 5777-5784.
Denning GM, Wollenwebber LA, Railsback MA, Cox CD, Stoll LL, Britigan BE. Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells. Infection and Immunity. 1998 Dec 1;66(12):5777-5784.
Denning, Gerene M. ; Wollenwebber, Laura A. ; Railsback, Michelle A. ; Cox, Charles D. ; Stoll, Lynn L. ; Britigan, Bradley E. / Pseudomonas pyocyanin increases interleukin-8 expression by human airway epithelial cells. In: Infection and Immunity. 1998 ; Vol. 66, No. 12. pp. 5777-5784.
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