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

Suwako Fujigaki, Kuniaki Saito, Kenji Sekikawa, Shigenobu Tone, Osamu Takikawa, Hidehiko Fujii, Hisayasu Wada, Akio Noma, Mitsuru Seishima

Research output: Contribution to journalArticle

164 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2313-2318
Number of pages6
JournalEuropean Journal of Immunology
Volume31
Issue number8
DOIs
Publication statusPublished - 06-09-2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology

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