Chemioxyexcitation (ΔpO2/ROS)-dependent release of IL-1β, IL-6 and TNF-α: Evidence of cytokines as oxygen-sensitive mediators in the alveolar epithelium

John J. E. Haddad (Lead / Corresponding author), Bared Safieh-Garabedian, Nayef E. Saadé, Salim A. Kanaan, Stephen C. Land

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)


The signalling mechanisms in oxidative stress mediated by cytokines in the perinatal alveolar epithelium are not well known. In an in vitro model of fetal alveolar type II epithelial cells, we investigated the profile of cytokines in response to ascending ΔpO2 regimen (oxyexcitation). The peak of TNF-α (4 h) preceded IL-1β and IL-6 (6-9 h), indicating a positive feedback autocrine loop confirmed by exogenous rmTNF-α. Reactive oxygen species (ROS) induced a dose-dependent release of cytokines, an effect specifically obliterated by selective antioxidants of the hydroxyl radical (·OH) and superoxide anion (O2 -). Actinomycin and cycloheximide blocked the induced production of cytokines, implicating transcriptional and translational control. Whilst the dismutating enzymes superoxide dismutase (SOD) and catalase were ineffective in reducing ROS-induced cytokines, MnP, a cell-permeating SOD mimetic, abrogated xanthine/xanthine oxidase-dependent cytokine release. Desferrioxamine mesylate, which inhibits the iron-catalysed generation of OH via the Fenton reaction, exhibited a mild effect on the release of cytokines. Dynamic variation in alveolar pO2 constitutes a potential signalling mechanism within the perinatal lung allowing upregulation of cytokines in an ROS-dependent manner.

Original languageEnglish
Pages (from-to)138-147
Number of pages10
Issue number3
Publication statusPublished - 7 Feb 2001


  • Antioxidant
  • Bronchopulmonary dysplasia
  • Cytokine
  • Development
  • Pathophysiology
  • Reactive oxygen species
  • Redox equilibrium

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology


Dive into the research topics of 'Chemioxyexcitation (ΔpO2/ROS)-dependent release of IL-1β, IL-6 and TNF-α: Evidence of cytokines as oxygen-sensitive mediators in the alveolar epithelium'. Together they form a unique fingerprint.

Cite this