scholarly journals Enhanced anti-tumour activity of carmustine (BCNU) with tumour necrosis factor in vitro and in vivo

1990 ◽  
Vol 62 (5) ◽  
pp. 776-780 ◽  
Author(s):  
AL Jones ◽  
JL Millar ◽  
BC Millar ◽  
B Powell ◽  
P Selby ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Anti Tumour Activity ◽  
Tumour Activity ◽  
Necrosis Factor

THE IMMUNOSUPPRESSANT STEROID CHOLESTERYLPHOSPHOSERINE INHIBITS TUMOUR NECROSIS FACTOR-α SECRETION IN VITRO AND IN VIVO

Cytokine ◽  
2000 ◽  
Vol 12 (6) ◽  
pp. 770-773 ◽  
Author(s):  
Laura Facci ◽  
Federico Cusinato ◽  
Alessandro Negro ◽  
Giovanni Monastra ◽  
Anna Signorelli ◽  
...  
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
Necrosis Factor

The effects of tumour necrosis factor on host—parasite relations in murine Mesocestoides corti (Cestoda) infection

Parasitology ◽  
1992 ◽  
Vol 105 (3) ◽  
pp. 453-459 ◽  
Author(s):  
P. Jenkins ◽  
S. Spiers ◽  
J. B. Dixon ◽  
S. D. Carter ◽  
S. May
Keyword(s):  
Tumour Necrosis Factor ◽  
Post Infection ◽  
Tumour Necrosis ◽  
Fold Increase ◽  
Peritoneal Macrophages ◽  
Hepatic Necrosis ◽  
Peritoneal Cells ◽  
Necrosis Factor

SUMMARYThe regulatory role of tumour necrosis factor (TNF) was investigated in murine infection with tetrathyridia of Mesocestoides corti. Recombinant TNFα reduced macrophage larvicidal activity in vitro. M. corti primed mice for TNF release in response to bacterial lipopolysaccharide (LPS) in vivo. TNF activity was amplified 100-fold at 14 days post-infection (p.i.), with a further rise at day 28 p.i. Maximal inflammatory reaction was observed histologically in the liver at the height of TNF activity. Hepatic necrosis was located within inflammatory foci, but not within the vicinity of the parasite itself, suggesting that TNF may contribute to the pathogenesis of infection. Peritoneal cells from infected mice, when stimulated with tetrathyridia in vitro, showed a 4-fold increase in TNFα activity at day 14 p.i. However, when peritoneal cells were stimulated with LPS in vitro, a marked increase in TNFα secretion was observed at 2 months post-infection followed by a slow decline. It is suggested that impaired macrophage effector function, previously attributed to endogenous endotoxin, which gains access to peritoneal macrophages through an inability of the liver to detoxify endotoxin, may be mediated through TNFα.

scholarly journals Regulation of lipoprotein lipase activity and mRNA content in rat epididymal adipose tissue in vitro by recombinant tumour necrosis factor

1990 ◽  
Vol 269 (1) ◽  
pp. 123-126 ◽  
Author(s):  
A G Mackay ◽  
J D Oliver ◽  
M P Rogers
Keyword(s):  
Adipose Tissue ◽  
Tumour Necrosis Factor ◽  
Lipoprotein Lipase ◽  
Tumour Necrosis ◽  
Epididymal Adipose Tissue ◽  
Mrna Levels ◽  
Isolated Adipocytes ◽  
Necrosis Factor

Tumour necrosis factor (TNF) has previously been shown to decrease lipoprotein lipase (LPL) activity and mRNA levels in 3T3-L1 cells and in adipose tissue from rats and guinea pigs when injected in vivo, but not to alter LPL activity in human adipocytes incubated in vitro. The effect of recombinant human TNF on LPL activity and mRNA levels in rat epididymal adipose tissue incubated in vitro was examined. LPL activity and mRNA levels fell in adipose tissue taken from fed rats and incubated in Krebs-Henseleit bicarbonate medium with glucose. The addition of insulin and dexamethasone prevented these falls. TNF (400 ng/ml) produced a fall of approx. 50% in LPL activity after 2 h of incubation and of approx. 30% in LPL mRNA levels after 3 h. TNF did not decrease LPL activity in isolated adipocytes. These results demonstrate that rat adipose tissue incubated in vitro is responsive to TNF whereas isolated adipocytes are not.

scholarly journals Blocking connexin43 hemichannels protects mice against tumour necrosis factor-induced inflammatory shock

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tinneke Delvaeye ◽  
Maarten A. J. De Smet ◽  
Stijn Verwaerde ◽  
Elke Decrock ◽  
Aleksandra Czekaj ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Single Channel ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Intracellular Ca ◽  
Necrosis Factor

Abstract Upon intravenous injection of tumour necrosis factor (TNF) in mice, a systemic inflammatory response syndrome (SIRS) is initiated, characterized by an acute cytokine storm and induction of vascular hyperpermeability. Connexin43 hemichannels have been implicated in various pathological conditions, e.g. ischemia and inflammation, and can lead to detrimental cellular outcomes. Here, we explored whether targeting connexin43 hemichannels could alleviate TNF-induced endothelial barrier dysfunction and lethality in SIRS. Therefore, we verified whether administration of connexin43-targeting-peptides affected survival, body temperature and vascular permeability in vivo. In vitro, TNF-effects on connexin43 hemichannel function were investigated by single-channel studies and Ca2+-imaging. Blocking connexin43 hemichannels with TAT-Gap19 protected mice against TNF-induced mortality, hypothermia and vascular leakage, while enhancing connexin43 hemichannel function with TAT-CT9 provoked opposite sensitizing effects. In vitro patch-clamp studies revealed that TNF acutely activated connexin43 hemichannel opening in endothelial cells, which was promoted by CT9, and inhibited by Gap19 and intracellular Ca2+-buffering. In vivo experiments aimed at buffering intracellular Ca2+, and pharmacologically targeting Ca2+/calmodulin-dependent protein kinase-II, a known modulator of endothelial barrier integrity, demonstrated their involvement in permeability alterations. Our results demonstrate significant benefits of inhibiting connexin43 hemichannels to counteract TNF-induced SIRS-associated vascular permeability and lethality.

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