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

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.

Substrate specificity and inducibility of TACE (tumour necrosis factor α-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity

2003 ◽  
Vol 70 ◽  
pp. 39-52 ◽  
Author(s):  
Roy A. Black ◽  
John R. Doedens ◽  
Rajeev Mahimkar ◽  
Richard Johnson ◽  
Lin Guo ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Recent Work ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Transforming Growth Factor ◽  
Intrinsic Activity ◽  
Converting Enzyme ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Tumour necrosis factor α (TNFα)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor α, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

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