TY - JOUR
T1 - Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-γ-independent mechanism
AU - Fujigaki, Suwako
AU - Saito, Kuniaki
AU - Sekikawa, Kenji
AU - Tone, Shigenobu
AU - Takikawa, Osamu
AU - Fujii, Hidehiko
AU - Wada, Hisayasu
AU - Noma, Akio
AU - Seishima, Mitsuru
PY - 2001
Y1 - 2001
N2 - Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the L-tryptophan-kynurenine pathway, which converts an essential amino acid, L-tryptophan, to N-formylkynurenine. It has been speculated that IFN-γ is a dominant IDO inducer in vivo. The present study used IFN-γ or TNF-α gene-disrupted mice and IFN-γ antibody-treated mice to demonstrate that lipopolysaccharide (LPS)-induced systemic IDO is largely dependent on TNF-α rather than IFN-γ. IFN-γ-independent IDO induction was also demonstrated in vitro with LPS-stimulated monocytic THP-1 cells. These findings clearly indicate that there is an IFN-γ-independent mechanism of IDO induction in addition to the IFN-γ-dependent mechanism.
AB - Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme in the L-tryptophan-kynurenine pathway, which converts an essential amino acid, L-tryptophan, to N-formylkynurenine. It has been speculated that IFN-γ is a dominant IDO inducer in vivo. The present study used IFN-γ or TNF-α gene-disrupted mice and IFN-γ antibody-treated mice to demonstrate that lipopolysaccharide (LPS)-induced systemic IDO is largely dependent on TNF-α rather than IFN-γ. IFN-γ-independent IDO induction was also demonstrated in vitro with LPS-stimulated monocytic THP-1 cells. These findings clearly indicate that there is an IFN-γ-independent mechanism of IDO induction in addition to the IFN-γ-dependent mechanism.
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U2 - 10.1002/1521-4141(200108)31:8<2313::AID-IMMU2313>3.0.CO;2-S
DO - 10.1002/1521-4141(200108)31:8<2313::AID-IMMU2313>3.0.CO;2-S
M3 - Article
C2 - 11477543
AN - SCOPUS:0034850590
SN - 0014-2980
VL - 31
SP - 2313
EP - 2318
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 8
ER -