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

✍ Scribed by Suwako Fujigaki; Kuniaki Saito; Kenji Sekikawa; Shigenobu Tone; Osamu Takikawa; Hidehiko Fujii; Hisayasu Wada; Akio Noma; Mitsuru Seishima

• Book ID: 101386258
• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 109 KB
• Volume: 31
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(200108)31:8<2313::aid-immu2313>3.0.co;2-s

✦ Synopsis

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-gamma is a dominant IDO inducer in vivo. The present study used IFN-gamma or TNF-alpha gene-disrupted mice and IFN-gamma antibody-treated mice to demonstrate that lipopolysaccharide (LPS)-induced systemic IDO is largely dependent on TNF-alpha rather than IFN-gamma. IFN-gamma-independent IDO induction was also demonstrated in vitro with LPS-stimulated monocytic THP-1 cells. These findings clearly indicate that there is an IFN-gamma-independent mechanism of IDO induction in addition to the IFN-gamma-dependent mechanism.