Macrophage-mediated lysis of a β-cell line, tumour necrosis factor-α release from bacillus Calmette‒Guérin (BCG)-activated murine macrophages and interleukin-8 release from human monocytes are dependent on extracellular glutamine concentration and glutamine metabolism

1999 ◽  
Vol 96 (1) ◽  
pp. 89 ◽  
Author(s):  
Colin MURPHY ◽  
Philip NEWSHOLME
Keyword(s):  
Cell Line ◽  
Tumour Necrosis ◽  
Glutamine Metabolism ◽  
Human Monocytes ◽  
Bacillus Calmette Guerin ◽  
Tumour Necrosis Factor Α ◽  
Glutamine Concentration ◽  
Β Cell ◽  
Factor Α ◽  
Necrosis Factor

Macrophage-mediated lysis of a β-cell line, tumour necrosis factor-α release from bacillus Calmette–Gue´rin (BCG)-activated murine macrophages and interleukin-8 release from human monocytes are dependent on extracellular glutamine concentration and glutamine metabolism

1999 ◽  
Vol 96 (1) ◽  
pp. 89-97
Author(s):  
Colin MURPHY ◽  
Philip NEWSHOLME
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Cytokine Production ◽  
Glutamine Metabolism ◽  
Human Monocytes ◽  
Tumour Necrosis Factor Α ◽  
Glutamine Concentration ◽  
Β Cell ◽  
Factor Α ◽  
Necrosis Factor

Macrophages and monocytes are cells with a large capacity for cytokine production. Cytokines produced by these cells are not preformed and released upon stimulation, but must be transcribed and translated. Although much is known concerning the regulation of the latter processes at the molecular level, the role of exogenous amino acids in the secretory process has not been actively investigated. Glutamine is utilized by macrophages at a much faster rate than any other amino acid. The role for high rates of glutamine utilization in macrophages or monocytes is not fully understood. We demonstrate here that the rates of lipopolysaccharide-stimulated tumour necrosis factor-α secretion from bacillus Calmette–Guérin (BCG)-activated murine peritoneal macrophages and lipopolysaccharide-stimulated interleukin-8 production from human monocytes are dependent upon extracellular glutamine concentration. We also demonstrate that potent inhibition of cytokine production can be achieved by incubating macrophages or monocytes in the presence of the glutaminase inhibitor 6-diazo-5-oxo-norleucine. On co-culture of BCG-activated macrophages and the clonal pancreatic β-cell line BRIN-BD11, macrophage-specific β-cell death was significantly reduced on prior exposure of macrophages to 6-diazo-5-oxo-norleucine. Thus glutamine metabolism may be essential for generation of cytotoxic products from macrophages, including tumour necrosis factor-α.

Dietary beta-carotene supplementation modulates the production of tumour necrosis factor-α by human monocytes

1996 ◽  
Vol 24 (3) ◽  
pp. 387S-387S ◽  
Author(s):  
DAVID A. HUGHES ◽  
PAUL M. FINGLAS ◽  
ANTHONY J.A. WRIGHT ◽  
ABIGAEL C.J. PEERLESS ◽  
ANGELA L. BAILEY ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Beta Carotene ◽  
Human Monocytes ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Tumour necrosis factor α and IL-2 mRNA expression in leukaemia cells (LB) and in a leukaemia cell line (LBC)

1997 ◽  
Vol 56 ◽  
pp. 279
Author(s):  
M.J. Gravisaco ◽  
C. Mongini ◽  
M. Sanchez Lockhart ◽  
C. Waldner ◽  
E. Alvarez ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cell Line ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Leukaemia Cell ◽  
Leukaemia Cell Line ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Isolation and Characterization of the Fungal Metabolite 3-O-Methylviridicatin as an Inhibitor of Tumour Necrosis Factor α-Induced Human Immunodeficiency Virus Replication

1998 ◽  
Vol 9 (2) ◽  
pp. 149-155 ◽  
Author(s):  
A Heguy ◽  
P Cai ◽  
P Meyn ◽  
D Houck ◽  
S Russo ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Line ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Luciferase Reporter ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Immunodeficiency Virus ◽  
Factor Α ◽  
Necrosis Factor

The cytokine tumour necrosis factor α (TNF-α) has been shown to play a role in human immunodeficiency virus (HIV) replication by activating transcription of the provirus in both T cells and macrophages. Therefore, agents that block TNF-α-induced HIV expression could have therapeutic value in the treatment of AIDS. We have sought to identify antiviral agents that block TNF-α induction of HIV LTR-directed transcription, using a cell-based, virus-free assay system in automated high-throughput screening. HeLa cells were transfected with an HIV LTR–luciferase reporter plasmid and a stable line was isolated in which TNF-α increased luciferase production by two- to threefold. This cell line was used to screen approximately 15 000 fungal extracts. An inhibitory activity specific for TNF-α-induced HIV LTR transcription was observed in culture OS-F67406. The active component was isolated and identified as a known metabolite, 3-O-methylviridicatin, by NMR and mass spectrometry. No biological activity has been associated with this compound previously. This compound blocks TNF-α activation of the HIV LTR in the HeLa-based system, with an IC50 of 5 μM, and inhibited virus production in the OM-10.1 cell line, a model of chronic infection responsive to induction by TNF-α, with an IC50 of 2.5 μM.

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