TY - JOUR
T1 - Chemioxyexcitation (ΔpO2/ROS)-dependent release of IL-1β, IL-6 and TNF-α
T2 - Evidence of cytokines as oxygen-sensitive mediators in the alveolar epithelium
AU - Haddad, John J. E.
AU - Safieh-Garabedian, Bared
AU - Saadé, Nayef E.
AU - Kanaan, Salim A.
AU - Land, Stephen C.
PY - 2001/2/7
Y1 - 2001/2/7
N2 - 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.
AB - 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.
KW - Antioxidant
KW - Bronchopulmonary dysplasia
KW - Cytokine
KW - Development
KW - Pathophysiology
KW - Reactive oxygen species
KW - Redox equilibrium
UR - http://www.scopus.com/inward/record.url?scp=0035819453&partnerID=8YFLogxK
U2 - 10.1006/cyto.2000.0789
DO - 10.1006/cyto.2000.0789
M3 - Article
C2 - 11161456
AN - SCOPUS:0035819453
VL - 13
SP - 138
EP - 147
JO - Cytokine
JF - Cytokine
SN - 1043-4666
IS - 3
ER -