Oxidative modulation of the glutathione-redox couple enhances lipopolysaccharide-induced interleukin 12 P40 production by a mouse macrophage cell line, J774A.1.
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.
Komatsu
Hiroyoshi
H
Department of Immunology, School of Allied Health Sciences, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan. hkomatsu@cc.ahs.kitasato-u.ac.jp
Hoshino
Aki
A
Funayama
Manabu
M
Kawahara
Katsumasa
K
Obata
Fumiya
F
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002330:Carmustine / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis*; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D021122:Protein Subunits / Q000096:biosynthesis*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
D018906:Antineoplastic Agents, Alkylating; D053762:Interleukin-12 Subunit p40; D008070:Lipopolysaccharides; D016328:NF-kappa B; D021122:Protein Subunits; D018664:Interleukin-12; D005978:Glutathione; D010100:Oxygen; D002330:Carmustine