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Cytotechnology

, Volume 54, Issue 2, pp 107–113 | Cite as

Transcriptional regulation of indoleamine 2,3-dioxygenase (IDO) by tryptophan and its analogue

Down-regulation of the indoleamine 2,3-dioxygenase (IDO) transcription by tryptophan and its analogue
  • Takeaki OkamotoEmail author
  • Shigenobu Toné
  • Hiroaki Kanouchi
  • Chie Miyawaki
  • Sayuri Ono
  • Yohsuke Minatogawa
Original Research

Abstract

Indoleamine 2,3-dioxygenase (IDO; EC 1.13.11.42) is a rate-limiting enzyme involved in the catabolism of tryptophan, which is an essential amino acid. It is induced under pathological conditions, such as the presence of viral infections or tumour cells. This enzyme is induced by IFN-γ in the mouse rectal carcinoma cell line CMT-93. It is known that both 1-methyl-l-tryptophan (1-MT) and methylthiohydantoin-dl-tryptophan (MTH-trp) are tryptophan analogues, and are authentic inhibitors of the enzymatic activity of IDO. In this study, we examined the effects of both 1-MT and MTH-trp on the IFN-γ inducible IDO expression of CMT-93. As a result, the IFN-γ inducible IDO mRNA and the protein levels in CMT-93 were suppressed by 1-MT and MTH-trp, independently. Moreover, tryptophan (Trp), as a substrate of IDO, also suppressed IDO induction by IFN-γ at the transcriptional level. These results suggest that 1-MT and MTH-trp are as inhibitors of IDO enzymatic activity, and Trp suppresses IDO induction by IFN-γ at the transcriptional level.

Keywords

CMT-93 IFN-γ 1-Methyl-l-tryptophan Methylthiohydantoin-dl-tryptophan 

Abbreviations

IDO

Indoleamine 2,3-dioxygenase

IFN

Interferon

1-MT

1-Methyl-l-tryptophan

MTH-trp

Methylthiohydantoin-dl-tryptophan

Notes

Acknowledgements

This study was supported in part by Research Project Grants (Nos. 17-509 and 18-502) from Kawasaki Medical School.

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Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Takeaki Okamoto
    • 1
    Email author
  • Shigenobu Toné
    • 1
  • Hiroaki Kanouchi
    • 2
  • Chie Miyawaki
    • 1
  • Sayuri Ono
    • 1
  • Yohsuke Minatogawa
    • 1
  1. 1.Department of BiochemistryKawasaki Medical SchoolKurashikiJapan
  2. 2.Department of Veterinary Pathobiology, Faculty of AgricultureKagoshima UniversityKagoshimaJapan

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