Marked increases in hippocampal neuron indoleamine 2, 3-dioxygenase via IFN-gamma-independent pathway following transient global ischemia in mouse.
Indoleamine 2, 3-dioxygenase (IDO), which catabolizes L-tryptophan (L-TRP) to L-kynurenine (L-KYN), is an immunoregulatory factor that is up-regulated via an interferon-gamma (IFN-gamma)-dependent and/or -independent mechanism. In this study, we investigated the localization of IDO and whether induction of IDO expression is an IFN-gamma-dependent and/or -independent mechanism in the CNS after cerebral ischemia. The expressions of IDO protein and mRNA were investigated at different time points following cerebral ischemia using immunohistochemistry, immunofluorescence and RT-PCR. Hippocampal neuron IDO mRNA and immunohistochemical staining were significantly up-regulated 72h after transient global ischemia. Although IFN-gamma is a dominant inducer of IDO, hippocampal neuron IDO was clearly up-regulated in IFN-gamma KO mice. In summary, this is the first finding that up-regulation of IDO in hippocampal neurons after transient global ischemia occurs via INF-gamma-independent mechanisms.
Hoshi
Masato
M
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu City, Japan.
Saito
Kuniaki
K
Murakami
Yuki
Y
Taguchi
Ayako
A
Fujigaki
Hidetsugu
H
Tanaka
Ryo
R
Takemura
Masao
M
Ito
Hiroyasu
H
Hara
Akira
A
Seishima
Mitsuru
M
D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D006624:Hippocampus / Q000473:pathology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D007371:Interferon-gamma; D010751:Phosphopyruvate Hydratase