Characterization of an Indoleamine 2,3-Dioxygenase Induced by Gamma-Interferon in Cultured Human Fibroblasts
- 1 June 1986
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Interferon Research
- Vol. 6 (3) , 267-279
- https://doi.org/10.1089/jir.1986.6.267
Abstract
We have previously observed that gamma-interferon (IFN-γ) inhibited the growth of the intracellular protozoan parasite Toxoplasma gondii in cultured human fibroblasts and that this inhibition was related to the disappearance of tryptophan from the medium with the concomitant appearance of kynurenine and N-formylkynurenine. In this report, we show that IFN-γ induced an indoleamine 2,3-dioxygenase in human fibroblasts that converts tryptophan to N-formylkynurenine. The induction of this enzyme was a function of IFN-γ concentration over the range of 1 to at least 32 NIH reference units/ml. The induction was also a function of time, with the greatest increase in indoleamine 2,3-dioxygenase seen 8–24 h after treatment of cultures with IFN-γ. The induction of indoleamine 2,3-dioxygenase by IFN-γ was inhibited by treatment of the cultures with either actinomycin D or cycloheximide, and thus was dependent on both RNA and protein synthesis. The indoleamine 2,3-dioxygenase induced by IFN-γ appeared to differ from other mammalian enzymes that degrade tryptophan. It had a Km for tryptophan that was 100-fold lower than that for rat liver tryptophan 2,3-dioxygenase and its substrate specificity was narrower than that of rabbit intestine indoleamine 2,3-dioxygenase. N-Formylkynurenine formamidase, the enzyme that produces kynurenine, was a constitutive enzyme and its activity was not further increased by treatment of human fibroblasts with IFN-γ. The indoleamine 2,3-dioxygenase induced by IFN-γ did not appear to play a major role in the antiviral activity of IFN-γ in human fibroblasts.Keywords
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