scholarly journals Tryptophan Depletion Modulates Tryptophanyl-tRNA Synthetase-Mediated High-Affinity Tryptophan Uptake into Human Cells

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1423
Author(s):  
Takumi Yokosawa ◽  
Aomi Sato ◽  
Keisuke Wakasugi
Keyword(s):  
Interferon Γ ◽  
Trna Synthetase ◽  
Human Cells ◽  
Human Interferon ◽  
Tryptophan Depletion ◽  
The Novel ◽  
High Affinity ◽  
Uptake Assay ◽  
Ifn Γ ◽  
Metabolizing Enzyme

The novel high-affinity tryptophan (Trp)-selective transport system is present at elevated levels in human interferon-γ (IFN-γ)-treated and indoleamine 2,3-dioxygenase 1 (IDO1)-expressing cells. High-affinity Trp uptake into cells results in extracellular Trp depletion and immune suppression. We have previously shown that both IDO1 and tryptophanyl-tRNA synthetase (TrpRS), whose expression levels are increased by IFN-γ, have a crucial function in high-affinity Trp uptake into human cells. Here, we aimed to elucidate the relationship between TrpRS and IDO1 in high-affinity Trp uptake. We demonstrated that overexpression of IDO1 in HeLa cells drastically enhances high-affinity Trp uptake upon addition of purified TrpRS protein to uptake assay buffer. We also clarified that high-affinity Trp uptake by Trp-starved cells is significantly enhanced by the addition of TrpRS protein to the assay buffer. Moreover, we showed that high-affinity Trp uptake is also markedly elevated by the addition of TrpRS protein to the assay buffer of cells overexpressing another Trp-metabolizing enzyme, tryptophan 2,3-dioxygenase (TDO2). Taken together, we conclude that Trp deficiency is crucial for high-affinity Trp uptake mediated by extracellular TrpRS.

scholarly journals Mouse Macrophages Carrying Both Subunits of the Human Interferon-γ (IFN-γ) Receptor Respond to Human IFN-γ but Do Not Acquire Full Protection against Viral Cytopathic Effect

1996 ◽  
Vol 271 (51) ◽  
pp. 32659-32666 ◽  
Author(s):  
David Lembo ◽  
Paola Ricciardi-Castagnoli ◽  
Gottfried Alber ◽  
Laurence Ozmen ◽  
Santo Landolfo ◽  
...  
Keyword(s):  
Cytopathic Effect ◽  
Interferon Γ ◽  
Human Interferon ◽  
Mouse Macrophages ◽  
Ifn Γ ◽  
Full Protection ◽  
Viral Cytopathic Effect

Protein synthesis-dependent potentiation by thyroxine of antiviral activity of interferon-γ

1997 ◽  
Vol 273 (4) ◽  
pp. C1225-C1232 ◽  
Author(s):  
Hung-Yun Lin ◽  
Paul M. Yen ◽  
Faith B. Davis ◽  
Paul J. Davis
Keyword(s):  
Thyroid Hormone ◽  
Antiviral Activity ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Thyroid Hormone Receptor ◽  
Signal Transduction Pathway ◽  
Interferon Γ ◽  
Human Interferon ◽  
Transduction Pathway ◽  
Ifn Γ

We have studied the prenuclear signal transduction pathway by which thyroid hormone potentiates the antiviral activity of human interferon-γ (IFN-γ) in HeLa cells, which are deficient in thyroid hormone receptor (TR). The action of thyroid hormone was compared with that of milrinone, which has structural homologies with thyroid hormone.l-Thyroxine (T4), 3,5,3′-l-triiodothyronine (T3), and milrinone enhanced the antiviral activity of IFN-γ up to 100-fold, a potentiation blocked by cycloheximide. The 5′-deiodinase inhibitor 6- n-propyl-2-thiouracil did not block the T4 effect. 3,3′,5,5′-Tetraiodothyroacetic acid prevented the effect of T4 but not of milrinone. The effects of T4 and milrinone were blocked by inhibitors of protein kinases C (PKC) and A (PKA) and restored by PKC and PKA agonists; only the effect of T4 was blocked by genistein, a tyrosine kinase inhibitor. In separate models, milrinone was shown not to interact with nuclear TR-β. T4 potentiation of the antiviral activity of IFN-γ requires PKC, PKA, and tyrosine kinase activities but not traditional TR.

scholarly journals Daratumumab (Anti-CD38) for Treatment of Disseminated Nontuberculous Mycobacteria in a Patient With Anti–Interferon-γ Autoantibodies

2020 ◽  
Author(s):  
Sebastian Ochoa ◽  
Li Ding ◽  
Samantha Kreuzburg ◽  
Jennifer Treat ◽  
Steven M Holland ◽  
...  
Keyword(s):  
Nontuberculous Mycobacteria ◽  
Interferon Γ ◽  
The Novel ◽  
Mycobacterial Infections ◽  
Ifn Γ ◽  
Radiographic Improvement

Abstract Patients with autoantibodies to interferon-γ (IFN-γ) may develop severe nontuberculous mycobacterial infections. We describe the novel use of daratumumab in a patient with autoantibodies to IFN-γ who had progressive infection, resulting in clinical and radiographic improvement.

scholarly journals Tryptophanyl-tRNA synthetase mediates high-affinity tryptophan uptake into human cells

2018 ◽  
Vol 293 (22) ◽  
pp. 8428-8438 ◽  
Author(s):  
Miki Miyanokoshi ◽  
Takumi Yokosawa ◽  
Keisuke Wakasugi
Keyword(s):  
Trna Synthetase ◽  
Human Cells ◽  
High Affinity ◽  
Tryptophan Uptake

scholarly journals Nitric Oxide-Mediated Regulation of Gamma Interferon-Induced Bacteriostasis: Inhibition and Degradation of Human Indoleamine 2,3-Dioxygenase

2004 ◽  
Vol 72 (5) ◽  
pp. 2723-2730 ◽  
Author(s):  
Christian Hucke ◽  
Colin R. MacKenzie ◽  
Koku D. Z. Adjogble ◽  
Osamu Takikawa ◽  
Walter Däubener
Keyword(s):  
Nitric Oxide ◽  
Gene Transcription ◽  
Kynurenine Pathway ◽  
Gamma Interferon ◽  
Human Cells ◽  
Epithelial Cell Line ◽  
Tryptophan Depletion ◽  
No Production ◽  
Indoleamine 2,3 Dioxygenase ◽  
Ifn Γ

ABSTRACT Tryptophan depletion resulting from indoleamine 2,3-dioxygenase (IDO) activity within the kynurenine pathway is one of the most prominent gamma interferon (IFN-γ)-inducible antimicrobial effector mechanisms in human cells. On the other hand, nitric oxide (NO) produced by the inducible isoform of NO synthase (iNOS) serves a more immunoregulatory role in human cells and thereby interacts with tryptophan depletion in a number of ways. We investigated the effects of NO on IDO gene transcription, protein synthesis, and enzyme activity as well as on IDO-mediated bacteriostasis in the human epithelial cell line RT4. IFN-γ-stimulated RT4 cells were able to inhibit the growth of Staphylococcus aureus in an IDO-mediated fashion, and this bacteriostatic effect was abolished by endogenously produced NO. These findings were supported by experiments which showed that IDO activity in extracts of IFN-γ-stimulated cells is inhibited by the chemical NO donors diethylenetriamine diazeniumdiolate, S-nitroso-l-cysteine, and S-nitroso-N-acetyl-d,l-penicillamine. Furthermore, we found that both endogenous and exogenous NO strongly reduced the level of IDO protein content in RT4 cells. This effect was not due to a decrease in IDO gene transcription or mRNA stability. By using inhibitors of proteasomal proteolytic activity, we showed that NO production led to an accelerated degradation of IDO protein in the proteasome. This is the first report, to our knowledge, that demonstrates that the IDO is degraded by the proteasome and that NO has an effect on IDO protein stability.

scholarly journals Human Interferon-γ(IFN-γ) Containing Cells Bear Various Surface Phenotypic Markers

1986 ◽  
Vol 30 (10) ◽  
pp. 1049-1059 ◽  
Author(s):  
Isamu Sugawara ◽  
Hiroshi Kitagawa ◽  
Hirofumi Inagaki ◽  
Mark De Ley ◽  
Akio Fukuda
Keyword(s):  
Interferon Γ ◽  
Human Interferon ◽  
Phenotypic Markers ◽  
Ifn Γ

A Bivalent Immunoadhesin of the Human Interferon-γ Receptor Is an Effective Inhibitor of IFN-γ Activity

1995 ◽  
Vol 15 (12) ◽  
pp. 1111-1115 ◽  
Author(s):  
DIETER MOOSMAYER ◽  
ELKE GERLACH ◽  
ROLAND HAUFF ◽  
PASCALE BECKER ◽  
BODO BROCKS ◽  
...  
Keyword(s):  
Interferon Γ ◽  
Human Interferon ◽  
Effective Inhibitor ◽  
Ifn Γ

scholarly journals High Throughput Screening for Human Interferon-y Production Inhibitor Using Homogenous Time-Resolved Fluorescence

2000 ◽  
Vol 5 (4) ◽  
pp. 263-268 ◽  
Author(s):  
Koji Enomoto ◽  
Yuko Aono ◽  
Takashi Mitsugi ◽  
Koji Takahashi ◽  
Ryuji Suzuki ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Culture Supernatant ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Human Interferon ◽  
Time Resolved Fluorescence ◽  
Time Resolved ◽  
Ifn Γ

An immunoassay for interferon-γ (IFN-γ) using homogeneous time-resolved fluorescence (HTRF) has been developed. In this assay, IFN-γ can be detected by simply adding a mixture of three reagents-biotinylated polyclonal antibody, europium cryptate (fluorescence donor, EuK)-labeled monoclonal antibody, and crosslinked allophycocyanin (fluorescence acceptor, XL665) conjugated with streptavidin-and then measuring the time-resolved fluorescence. The detection limit of IFN-γ by the proposed method is about 625 pg/ml. We applied the method to the detection of IFN-γ secreted from NK3.3 cells and employed it in high throughput screening for IFN-γ production inhibitors. With this screening format, IFN-γ can be measured by directly adding the above reagents to microplate wells where NK3.3 cells are being cultured and stimulated with interleukin-12. This "in situ" immunoassay requires only pipetting reagents, with no need to transfer the culture supernatant to another microplate or wash the plate. Therefore, this screening format makes possible full automation of cell-based immunoassay, thus reducing cost and experimental time while increasing accuracy and throughput.

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