Tumour necrosis factor‐α stimulates human neutrophils to release preformed activin A

2011 ◽  
Vol 89 (8) ◽  
pp. 889-896 ◽  
Author(s):  
Yi Chen ◽  
Hui Wu ◽  
Wendy R Winnall ◽  
Kate L Loveland ◽  
Yogeshwar Makanji ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Activin A ◽  
Human Neutrophils ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

Characterization of the survival effect of tumour necrosis factor-α in human neutrophils

2004 ◽  
Vol 32 (3) ◽  
pp. 456-460 ◽  
Author(s):  
S.R. Walmsley ◽  
A.S. Cowburn ◽  
A. Sobolewski ◽  
J. Murray ◽  
N. Farahi ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Time Course ◽  
Human Neutrophils ◽  
Tumour Necrosis Factor Α ◽  
Peripheral Blood Mononuclear ◽  
Gm Csf ◽  
Factor Α ◽  
Survival Effect ◽  
Necrosis Factor

Granulocyte apoptosis has been proposed as a fundamental, injury-limiting granulocyte-clearance mechanism. As such, inhibition of this process may prevent the resolution of inflammation. Our previous studies have shown that TNFα (tumour necrosis factor-α) has a bi-modal influence on the rate of constitutive neutrophil apoptosis in vitro, causing early acceleration and late inhibition of this process. The pro-apoptotic effect is uniquely TNFR1 (TNF receptor 1) and TNFR2-dependent and the latter survival process is mediated via phosphoinositide 3-kinase and NF-κB (nuclear factor-κB) activation. In the present study, we show that, in contrast with GM-CSF (granulocyte/macrophage colony-stimulating factor), the delayed addition (i.e. at 6 h) of TNFα increases its survival effect despite substantial loss of neutrophil TNFR1 and TNFR2 at that time. This paradox was resolved using PBMC (peripheral blood mononuclear cell)-deplete and 5% PBMC-replete neutrophil cultures, where the enhanced survival effect observed after delayed TNFα addition was shown to be PBMC-dependent. TNFR2-blocking antibodies had no effect on the late survival effect of TNFα, implying a TNFR1-dependent process. Finally, I-κBα (inhibitory κB-α) and NF-κB time-course studies demonstrated that the survival effects of both GM-CSF and TNFα could be explained by maintenance of functional NF-κB.

Regulation of activin A release from murine bone marrow-derived neutrophil precursors by tumour necrosis factor-α and insulin

Cytokine ◽  
2013 ◽  
Vol 61 (1) ◽  
pp. 199-204 ◽  
Author(s):  
Hui Wu ◽  
Yi Chen ◽  
Wendy R. Winnall ◽  
David J. Phillips ◽  
Mark P. Hedger
Keyword(s):  
Bone Marrow ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Activin A ◽  
Tumour Necrosis Factor Α ◽  
Murine Bone Marrow ◽  
Factor Α ◽  
Necrosis Factor

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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