scholarly journals Regulation of lipoprotein lipase mRNA content in 3T3-L1 cells by tumour necrosis factor

1988 ◽  
Vol 249 (3) ◽  
pp. 765-769 ◽  
Author(s):  
P Cornelius ◽  
S Enerback ◽  
G Bjursell ◽  
T Olivecrona ◽  
P H Pekala
Keyword(s):  
Tumour Necrosis Factor ◽  
Lipoprotein Lipase ◽  
Tumour Necrosis ◽  
Time Course ◽  
Northern Blot Analysis ◽  
Cdna Probe ◽  
Mrna Content ◽  
Normal Increase ◽  
Delayed Time ◽  
Necrosis Factor

Tumour necrosis factor (TNF) was previously shown to suppress lipoprotein lipase (LPL) synthesis and activity in 3T3-L1 adipocytes. The present study examined the effect of TNF on amounts of mRNA for LPL in 3T3-L1 cells. Northern-blot analysis of polyadenylated RNA using a cDNA probe to guinea-pig LPL identified two predominant species of LPL message, 3.7 and 3.9 kilobases in size. The steady-state amounts of these mRNAs increased 10-fold upon expression of the adipocyte phenotype. A single dose of 1.5 nM-TNF decreased LPL mRNA by approx. 60% in 17 h with a corresponding decrease in LPL activity, an effect that was reversed 48 h after exposure to TNF. The results demonstrate that TNF reversibly down-regulates LPL mRNA in fully differentiated 3T3-L1 adipocytes. Cells induced to differentiate in the presence of 1.5 nM-TNF exhibited a delayed time course for development of the adipocyte phenotype, as judged by attenuation of the normal increase in LPL mRNA that occurs with differentiation.

scholarly journals Regulation of lipoprotein lipase synthesis in 3T3-L1 adipocytes by cachectin Further proof for identity with tumour necrosis factor

1986 ◽  
Vol 240 (2) ◽  
pp. 601-604 ◽  
Author(s):  
S R Price ◽  
T Olivecrona ◽  
P H Pekala
Keyword(s):  
Protein Synthesis ◽  
Conditioned Medium ◽  
Tumour Necrosis Factor ◽  
Lipoprotein Lipase ◽  
Tumour Necrosis ◽  
Secretory Protein ◽  
Necrosis Factor ◽  
Precipitable Protein

We investigated the mechanism by which the endotoxin-induced macrophage secretory protein cachectin is able to suppress the activity of lipoprotein lipase in 3T3-L1 adipocytes. The loss in activity results from an effect on the synthesis of the enzyme, as determined by a decreased incorporation of [35S]methionine into immunoprecipitable lipoprotein lipase. The results were nearly identical whether crude conditioned medium or a highly purified preparation was utilized as a source of cachectin. [35S]Methionine incorporation into acid-precipitable protein was minimally affected by purified cachectin, suggesting that the suppression of the lipoprotein lipase was not due to a general suppression of protein synthesis. These results, taken together with our previous work, provide additional evidence that cachectin and tumour necrosis factor are functionally identical.

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.

Interleukin-1 and tumour necrosis factor cause hypotension in the conscious rabbit

1988 ◽  
Vol 75 (3) ◽  
pp. 251-255 ◽  
Author(s):  
J. R. Weinberg ◽  
D. J. M. Wright ◽  
A. Guz
Keyword(s):  
Blood Pressure ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Time Course ◽  
Interleukin 1 ◽  
Cardiovascular Effects ◽  
Study Groups ◽  
Fluid Loss ◽  
Conscious Rabbit ◽  
Necrosis Factor

1. The cardiovascular effects of intravenous injections of interleukin-1 (IL-1) and tumour necrosis factor (TNF) have been investigated in the conscious rabbit. They have been compared with the effects of bacterial lipopolysaccharide (LPS) because both IL-1 and TNF are released from macrophages by LPS. 2. IL-1, TNF and Escherichia coli J5-LPS all caused hypotension when given intravenously in a dose with low mortality. The time course of the hypotension caused by IL-1 and LPS was similar, although the maximal fall in mean blood pressure occurred earlier after IL-1. TNF produced a more sustained fall in blood pressure. Hypotension was not accompanied by a compensatory tachycardia after any of the test substances. Hypotension was associated with a fever after TNF, hypothermia after LPS and no significant change in temperature after IL-1. 3. The packed cell volume did not change during hypotension in any of the study groups, implying that the hypotension was not due to fluid loss resulting from increased capillary permeability. 4. IL-1 and TNF are candidates for the role of effectors of LPS-induced hypotension.

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.

Anti-Tumour Necrosis Factor-α Treatment Interferes with Changes in Lipid Metabolism in a Tumour Cachexia Model

1994 ◽  
Vol 87 (3) ◽  
pp. 349-355 ◽  
Author(s):  
Neus Carbó ◽  
Paola Costelli ◽  
Luciana Tessitore ◽  
Gregory J. Bagby ◽  
Francisco J. López-Soriano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Tumour Necrosis Factor ◽  
Lipoprotein Lipase ◽  
Lipase Activity ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Lipoprotein Lipase Activity ◽  
Tumour Bearing ◽  
Factor Α ◽  
Necrosis Factor

1. Rats bearing the Yoshida ascites hepatoma AH-130 showed an important decrease in white adipose tissue lipoprotein lipase activity as compared with non-tumour bearing rats. This was associated with a lower adipose tissue mass, as estimated from the weight of the lumbar fat-pads. Conversely, lipoprotein lipase activity was markedly increased in brown adipose tissue and heart. 2. These changes were associated with a distinct hyperlipaemia, essentially manifested as an increase in circulating triacylglycerol levels, whereas no changes were observed in glycaemia. 3. Tumour-bearing rats were treated with a polyclonal anti-murine tumour necrosis factor-α antibody or with a non-immune IgG preparation. Control animals were either untreated or received a nonimmune IgG preparation. Anti-tumour necrosis factor-α treatment resulted in a significant increase in lipoprotein lipase activity in white adipose tissue in animals bearing a tumour growing exponentially (day 4 after inoculation) as compared with the animals receiving a non-immune goat IgG preparation. In addition, animals bearing an stationary tumour (day 7 after inoculation) and submitted to anti-tumour necrosis factor-α treatment had a higher adipose tissue lipoprotein lipase activity as compared with the IgG- or the non-treated groups. Correspondingly, circulating triacylglycerol levels were markedly decreased, with a lower hyperlipaemia than in control tumour-bearing rats. 4. These observations suggest that tumour necrosis factor-α is involved in activating the lipid metabolic changes that develop in rats after transplantation of a fast-growing tumour.

Dietary fatty acids influence the appearance of tumour necrosis factor-α receptors on adipocytes following an immune challenge

2000 ◽  
Vol 84 (3) ◽  
pp. 387-392 ◽  
Author(s):  
Hilary A. MacQueen ◽  
Dawn Sadler ◽  
Christine Mattacks
Keyword(s):  
Fatty Acids ◽  
Tumour Necrosis Factor ◽  
Sunflower Oil ◽  
Tumour Necrosis ◽  
Time Course ◽  
Dietary Fatty Acids ◽  
Tumour Necrosis Factor Α ◽  
Inflammatory Immune Response ◽  
Factor Α ◽  
Necrosis Factor

Rats were fed from weaning on chow supplemented with suet or sunflower oil (10 % (w/w) each). The appearance of receptors for tumour necrosis factor-α on perinodal adipocytes from the popliteal depot following a subcutaneous injection of bacterial lipopolysaccharide was examined. In rats fed on sunflower oil-supplemented chow receptors appeared at a time similar to that described in rats fed unsupplemented chow, but in rats fed on chow supplemented with suet receptor appearance was significantly delayed. The popliteal adipocytes were found to contain different proportions of fatty acids as assessed by GLC. These preliminary results suggest that the fatty acid component of the diet can, by influencing the triacylglycerol-fatty acids within adipocytes, directly alter the time course of an early inflammatory immune response.

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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