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Redox regulation of pro-inflammatory cytokines and IkappaB-alpha/NF-kappaB nuclear translocation and activation.
Biochem Biophys Res Commun. 2002 Aug 30; 296(4):847-56.BB

Abstract

Reduction-oxidation (redox) state constitutes such a potential signaling mechanism for the regulation of an inflammatory signal associated with oxidative stress. Exposure of alveolar epithelial cells to ascending DeltapO(2) regimen+/-reactive oxygen species (ROS)-generating systems induced a dose-dependent release of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. Similarly, the Escherichia coli-derived lipopolysaccharide-endotoxin (LPS) up-regulated cytokine biosynthesis in a dose- and time-dependent manner. Irreversible inhibition of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutathione (GSH), by L-buthionine-(S,R)-sulfoximine (BSO), induced the accumulation of ROS and augmented DeltapO(2) and LPS-mediated release of cytokines. Analysis of the molecular mechanism implicated revealed an inhibitory-kappaB (IkappaB-alpha)/nuclear factor-kappaB (NF-kappaB)-independent pathway in mediating redox-dependent regulation of inflammatory cytokines. BSO stabilized cytosolic IkappaB-alpha and down-regulated its phosphorylation, thereby blockading NF-kappaB activation, yet it augmented cytokine secretion. Glutathione depletion is associated with the augmentation of oxidative stress-mediated inflammatory state in a ROS-dependent mechanism and the IkappaB-alpha/NF-kappaB pathway is redox-sensitive but differentially involved in regulating redox-dependent regulation of cytokines.

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Authors+Show Affiliations

Haddad JJ
Oxygen Signaling Group, Center for Research into Human Development, Tayside Institute of Child Health, Faculty of Medicine, Ninewells Hospital & Medical School, University of Dundee, Scotland, UK [corrected]. johnjhaddad@yahoo.co.uk

MeSH

Active Transport, Cell NucleusAnimalsAntioxidantsBlotting, WesternCell NucleusCells, CulturedCytokinesDNA-Binding ProteinsDose-Response Relationship, DrugEnzyme-Linked Immunosorbent AssayEpithelial CellsEscherichia coliGlutamate-Cysteine LigaseGlutathioneHydrogen PeroxideI-kappa B ProteinsInterleukin-1Interleukin-6LipopolysaccharidesNF-KappaB Inhibitor alphaNF-kappa BOxidation-ReductionOxidative StressOxygenProtein TransportRatsRats, Sprague-DawleyReactive Oxygen SpeciesSignal TransductionTemperatureTime FactorsUp-Regulation

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12200125

Citation

Haddad, John J.. "Redox Regulation of Pro-inflammatory Cytokines and IkappaB-alpha/NF-kappaB Nuclear Translocation and Activation." Biochemical and Biophysical Research Communications, vol. 296, no. 4, 2002, pp. 847-56.
Haddad JJ. Redox regulation of pro-inflammatory cytokines and IkappaB-alpha/NF-kappaB nuclear translocation and activation. Biochem Biophys Res Commun. 2002;296(4):847-56.
Haddad, J. J. (2002). Redox regulation of pro-inflammatory cytokines and IkappaB-alpha/NF-kappaB nuclear translocation and activation. Biochemical and Biophysical Research Communications, 296(4), 847-56.
Haddad JJ. Redox Regulation of Pro-inflammatory Cytokines and IkappaB-alpha/NF-kappaB Nuclear Translocation and Activation. Biochem Biophys Res Commun. 2002 Aug 30;296(4):847-56. PubMed PMID: 12200125.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Redox regulation of pro-inflammatory cytokines and IkappaB-alpha/NF-kappaB nuclear translocation and activation. A1 - Haddad,John J, PY - 2002/8/30/pubmed PY - 2002/10/12/medline PY - 2002/8/30/entrez SP - 847 EP - 56 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 296 IS - 4 N2 - Reduction-oxidation (redox) state constitutes such a potential signaling mechanism for the regulation of an inflammatory signal associated with oxidative stress. Exposure of alveolar epithelial cells to ascending DeltapO(2) regimen+/-reactive oxygen species (ROS)-generating systems induced a dose-dependent release of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. Similarly, the Escherichia coli-derived lipopolysaccharide-endotoxin (LPS) up-regulated cytokine biosynthesis in a dose- and time-dependent manner. Irreversible inhibition of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of glutathione (GSH), by L-buthionine-(S,R)-sulfoximine (BSO), induced the accumulation of ROS and augmented DeltapO(2) and LPS-mediated release of cytokines. Analysis of the molecular mechanism implicated revealed an inhibitory-kappaB (IkappaB-alpha)/nuclear factor-kappaB (NF-kappaB)-independent pathway in mediating redox-dependent regulation of inflammatory cytokines. BSO stabilized cytosolic IkappaB-alpha and down-regulated its phosphorylation, thereby blockading NF-kappaB activation, yet it augmented cytokine secretion. Glutathione depletion is associated with the augmentation of oxidative stress-mediated inflammatory state in a ROS-dependent mechanism and the IkappaB-alpha/NF-kappaB pathway is redox-sensitive but differentially involved in regulating redox-dependent regulation of cytokines. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/12200125/Redox_regulation_of_pro_inflammatory_cytokines_and_IkappaB_alpha/NF_kappaB_nuclear_translocation_and_activation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006291X02009476 DB - PRIME DP - Unbound Medicine ER -
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