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• W2055144772 abstract "Interferon-γ (IFN-γ)-induced, indoleamine dioxygenase-catalyzed tryptophan catabolism was studied in cultured human foreskin fibroblasts using the increase in cellular kynurenine synthesis as an index of gene expression. The time courses of the inhibition of IFN-γ-induced kynurenine synthesis by actinomycin D and cycloheximide showed that the indoleamine dioxygenase gene was transcribed as early as 2 h and translated as early as 5 h after initiation of IFN treatment. Expression was completely inhibited by the Ser/Thr kinase inhibitor, H-7 (66 μM), during the First 2 h after IFN-γ treatment. Prolonged pretreatment of cells with high concentrations of staurosporine (380 nM) or genestein (610 μM) inhibited expression by 38% and 53%, respectively. Genestein also inhibited expression when it was added to cultures between 8 and 24 h after IFNγ treatment. The expression of kynurenine synthesis was inhibited by A23817 during the first 4 h after IFN treatment by mechanisms that were independent of cyclooxygenase, calmodulin, and calcineurin. Exogenous gangliosides (bovine brain gangliosides and purified GM1) inhibited IDO expression throughout the first 24 h after IFN-γ treatment by mechanisms that did not involve effects on Ca2+ channels. Other biologic response modifiers, including phorbol myristic acetate, arachidonic acid, lipopolysaccharide, analogs of cAMP and cGMP, W-7, and sphingosine, did not induce IDO in the absence of IFN-γ, nor did they modulate IFN-γ-induced expression. These results indicate that the expression of kynurenine synthesis is modulated at the transcriptional and posttranscriptional levels by protein tyrosine kinase and by a Ser/Thr kinase with properties distinctly different from those of conventional protein kinase C. The capacity for attenuation of this IFN-γinduced response over its entire time course by many effectors and through multiple cellular signaling pathways may represent a mechanism for finetuning the level of oxidative tryptophan metabolism to meet the needs of a particular cytostatic or antiproliferative response." @default.
• W2055144772 created "2016-06-24" @default.
• W2055144772 creator A5086328017 @default.
• W2055144772 date "1998-07-01" @default.
• W2055144772 modified "2023-10-16" @default.
• W2055144772 title "Expression and Regulation of Interferon- γ-Induced Tryptophan Catabolism in Cultured Skin Fibroblasts" @default.
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• W2055144772 doi "https://doi.org/10.1089/jir.1998.18.509" @default.
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