title: Differential regulation of the human, interferon inducible tryptophanyl-tRNA synthetase by various cytokines in cell lines.
abstract: Cytokines regulate the expression of specific sets of proteins which mediate their biological effects. We have comprehensively delineated the regulation of the human tryptophanyl-tRNA synthetase (hWRS) by eight different cytokines (including IFNs) and poly(I).poly(C) in several cell lines. Six non-lymphoid cell lines were tested, and all of these produced human, IFN inducible hWRS (gamma 2) mRNA upon stimulation with IFN-gamma. In all these cell lines the level of gamma 2 mRNA increased 2-4 h after induction reaching a stable plateau after 8-12 h. The IFN-gamma induction of gamma 2 mRNA could be blocked by cycloheximide in human amniotic (AMA) cells, epithelial HeLa cells and HT1080 fibroblasts, but not in T98G glioblastoma cells. IFN-alpha and poly(I).poly(C) elicited small, transient gamma 2 responses in a few of the non-lymphoid cell lines, whereas none of the other six cytokines tested elicited a response. The six lymphoid cell lines tested did not show the same induction pattern. In the monocytic cells, THP-1, gamma 2 mRNA was highly induced by IFN-gamma, whereas in the B-cell line, Daudi, gamma 2 mRNA was transiently induced by IFN-alpha and poly(I).poly(C), and not by IFN-gamma. Altered mRNA turnover rate as a consequence of IFN-gamma treatment did not appear to play a significant role in the accumulation of gamma 2 transcript, since the stability essentially was the same in induced versus non-induced cells. We conclude that the hWRS gene is induced preferentially by IFN-gamma, and that the induction pattern resembles the one reported for the IFN induced enzyme, indoleamine 2,3-dioxygenase (IDO).
authors.affiliation: Department of Molecular Biology, University of Aarhus, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Fleckner
authors.forename: P M
authors.initials: PM
authors.lastname: Martensen
authors.forename: A B
authors.initials: AB
authors.lastname: Tolstrup
authors.forename: N O
authors.initials: NO
authors.lastname: Kjeldgaard
authors.forename: J
authors.initials: J
authors.lastname: Justesen
mesh_terms: D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007369:Interferon Inducers / Q000494:pharmacology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D014366:Tryptophan Oxygenase / Q000096:biosynthesis; D014369:Tryptophan-tRNA Ligase / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007369:Interferon Inducers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007378:Interleukins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003609:Dactinomycin; D007371:Interferon-gamma; D003513:Cycloheximide; D014366:Tryptophan Oxygenase; D014369:Tryptophan-tRNA Ligase