Pseudomonas pyocyanin inhibits cytokine-induced nitric oxide release by human airway epithelial cells

L. L. Stoll, G. M. Johnson, Y. Li, M. A. Railsback, B. E. Britigan, G. M. Denning

Research output: Contribution to journalArticlepeer-review

Abstract

Pseudomonas aeruginosa (PA) is an opportunistic bacterium associated with acute pneumonia in patients with hospital-acquired infections, and with chronic lung disease in cystic fibrosis patients. PA secretes numerous factors that may contribute to both acute and chronic forms of PA-associated lung disease We report here that one of these secretory factors, pyocyanin (PY), inhibits the ability of inflammatory cytokines to increase nitric oxide (NO) release by A549 human airway epithelial cells. Maximal inhibition occurs at 50 μM PY, and is reversible. This reversibility suggests that the inhibition does not represent nonspecific cytotoxicity by PY. Furthermore, studies using reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrate that PY exerts its effects, at least in part, by inhibiting increases in steady-state mRNA levels of inducible NO synthase (iNOS). However, the effect of PY on iNOS mRNA levels is significantly less than its effect on NO release. Moreover, partial inhibition is observed even if PY is added after maximal iNOS mRNA levels are achieved. These results suggest that PY may also inhibit NO formation or release at a step distal to induction of iNOS message, or may act as an NO scavenger. NO is a smooth muscle cell (SMQ relaxant released by airway epithelial cells in response to inflammatory cytokines (IFN-gamma, TNF-α, IL-1). Increased NO may be important in the inflammed lung as a means of counteracting the effects of mediators that are also released during inflammation, but that cause SMC contraction. If PY inhibits NO release, then this might contribute to the reduced lung function observed in PA-associated lung disease.

Original languageEnglish (US)
Pages (from-to)A137
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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