1993 Fiscal Year Final Research Report Summary
Molecular cloning of trans-acting factor cDNA for IFN-gamma-inducible indoleamine 2,3-dioxygenase
| Project/Area Number |
04680203
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
代謝生物化学
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| Research Institution | Osaka Bioscience Institute |
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Principal Investigator |
TAKIKAWA Osamu Osaka Bioscience Institute, Department of Cell Biology, Research Scientist, 第4研究部, 研究員 (70163342)
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| Co-Investigator(Kenkyū-buntansha) |
TONE Sigenobu Wakayama MEdical College Department of Biochemistry, Assistant Professor, 助手 (70211399)
YOSHIDA Ryotaro Osaka Bioscience Institute, Department of Cell Biology, Head, 第4研究部, 部長 (10124760)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Oxygenase / Interferon-gamma / Trans-acting factor / Signal transduction / Cytokine / Tryptophan metabolism |
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| Research Abstract |
Until 1992, we have isolated the gene of indoleamine 2,3-dioxygenase (IDO), an IFN-gamma-inducible tryptophan degrading enzyme, from human genomic DNA library using the IDO cDNA as a probe, and their restriction maps and partial nucleotide sequences were determined. The 5' flanking region contains IFN-stimulated response element (ISRE) and X-box like sequences. These sequences have a promoting activity for transcription of IDO mRNA.The IFN-gamma-mediated production of the IDO mRNA was suppressed by protein synthesis inhibitors, indicating an involvement of protein(s) newly synthesized in the induction of mRNA.The synthesis of the protein(s) occurred within 3h after the addition of IFN-gamma.
In 1993, we have examined the presence of trans-acting protein(s) for the enhancer element (ISRE and X-box) for transcription of IDO mRNA in nuclear or cytoplasmic extract of human lung fibroblasts (HEL), which exhibited the highest induction of IDO by the addition of IFN-gamma. On the other hand, the expression of IDO gene was inhibited strongly by herbimycin A, an inhibitor for tyrosine kinase, suggesting an implication of a tyrosine kinase in the enzyme induction. Northern blotting analysis indicated that the human IDO gene is expressed abundantly in the thymus in addition to the placenta, lung, and small intestine.
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