Lipopolysaccharide induction of indoleamine 2,3‐dioxygenase is mediated dominantly by an IFN‐γ‐independent mechanism

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 m...

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Bibliographic Details
Published in:European journal of immunology 2001-08, Vol.31 (8), p.2313-2318
Main Authors: Fujigaki, Suwako, Saito, Kuniaki, Sekikawa, Kenji, Tone, Shigenobu, Takikawa, Osamu, Fujii, Hidehiko, Wada, Hisayasu, Noma, Akio, Seishima, Mitsuru
Format: Article
Language:English
Subjects:
Animals
Antibodies - pharmacology
Cytokines - antagonists & inhibitors
Cytokines - physiology
Enzyme Induction - drug effects
g-Interferon
Gene Deletion
Humans
IFN‐γ
Indoleamine 2,3‐dioxygenase
Indoleamine-Pyrrole 2,3,-Dioxygenase
Interferon-gamma - antagonists & inhibitors
Interferon-gamma - genetics
Interferon-gamma - physiology
Lipopolysaccharide
lipopolysaccharides
Lipopolysaccharides - pharmacology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
N-formylkynurenine
RNA, Messenger - genetics
RNA, Messenger - metabolism
tryptophan
Tryptophan Oxygenase - genetics
Tryptophan Oxygenase - metabolism
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - genetics
Tumor Necrosis Factor-alpha - physiology
Citations: Items that this one cites
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Summary: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.
ISSN:0014-2980
1521-4141
DOI:10.1002/1521-4141(200108)31:8<2313::AID-IMMU2313>3.0.CO;2-S