Cysteine-dependent immune regulation by TRX and MIF/GIF family proteins.
Thioredoxin (TRX) superfamily proteins that contain a conserved redox-active site -Cys-Xa.a.-Xa.a.-Cys- includes proinflammatory cytokine, macrophage migration inhibiting factor (MIF) and the immune regulatory cytokine, glycosylation inhibiting factor (GIF) in which Cys-60 is cysteinylated. In this report, we have analyzed the functional interaction between TRX and MIF/GIF. The stable Jurkat T cell line transfected with human TRX gene (TRX-transfectant) was highly resistant to hydrogen peroxide-induced apoptosis, but not the cell line transfected with vector (mock-transfectant). The expression level of MIF/GIF protein of TRX-transfectant was lower than that of mock-transfectant. Conversely, the expression level of intracellular TRX protein in CD4(+)-T cells derived from MIF -/- mice were significantly higher than that from background BALB/c mice. These findings collectively suggest that oxidative stress-induced apoptosis on T lymphocytes might be protected by the reciprocal regulation of TRX and MIF/GIF expression.
Kondo
Norihiko
N
Department of Biological Responses, Institute of Virus Research, Kyoto University, Kyoto, Japan.
Ishii
Yasuyuki
Y
Son
Aoi
A
Sakakura-Nishiyama
Junko
J
Kwon
Yong-Won
YW
Tanito
Masaki
M
Nishinaka
Yumiko
Y
Matsuo
Yoshiyuki
Y
Nakayama
Toshinori
T
Taniguchi
Masaru
M
Yodoi
Junji
J
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D019746:Intramolecular Oxidoreductases; D019169:Jurkat Cells; D008222:Lymphokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D005810:Multigene Family / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013879:Thioredoxins / Q000276:immunology* / Q000378:metabolism
D008222:Lymphokines; D008263:Macrophage Migration-Inhibitory Factors; C013059:immunoglobulin-binding factors; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse; D003545:Cysteine