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Oxidative modulation of the glutathione-redox couple enhances lipopolysaccharide-induced interleukin 12 P40 production by a mouse macrophage cell line, J774A.1.

Authors
  • 1
Type
Published Article
Journal
Free Radical Research
1029-2470
Publisher
Informa UK (Taylor & Francis)
Publication Date
Volume
37
Issue
3
Pages
293–299
Identifiers
PMID: 12688424
Source
Medline

Abstract

Interleukin (IL)-12 plays a key role in determining the immune response pattern that results in maturation of Th0 to Th1 and Th2. To investigate the correlation between intracellular redox state and IL-12 production in macrophages, cells from the mouse cell line J774A.1 were treated with reagents modulating the glutathione-redox couple before stimulation with lipopolysaccharide (LPS). It was found that the glutathione reductase inhibitor, 1,3-bis (2-chloroethyl)-1-nitrosourea, markedly augmented LPS induced IL-12p40 production particularly when it was added for 24 h before LPS stimulation, whereas the glutathione-synthesis inhibitor, L-buthionine-(S,R)-sulfoximine, suppressed IL-12p40 production. The profile of IL-12p40 augmentation correlated well with the profile of intracellular glutathione oxidation (GSSG) and the activation profile of nuclear transcription factor kappaB (NF-kappaB), suggesting that GSSG is important in NF-kappaB activation which leads to IL-12p40 production. Our results indicate that the glutathione-redox couple plays an important role in the augmented production of IL-12p40 and thus in influencing immune response patterns.

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