scholarly journals Regulation of tumour necrosis factor-alpha release from human adipose tissue in vitro

1999 ◽  
Vol 163 (1) ◽  
pp. 33-38 ◽  
Author(s):  
CP Sewter ◽  
JE Digby ◽  
F Blows ◽  
J Prins ◽  
S O'Rahilly
Keyword(s):  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Tumour Necrosis Factor Alpha ◽  
Host Defence ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Isolated Adipocytes ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Stimulation Of

Tumour necrosis factor-alpha (TNF-alpha), secreted by cells of the macrophage-monocyte lineage, has a well established role in inflammation and host-defence. The more recent discovery that adipocytes also secrete TNF-alpha has led to a substantial body of research implicating this molecule in the insulin resistance of obesity. However, little is known about the normal regulation of TNF-alpha release from human adipose tissue. In particular, it is not known whether adipocyte production of TNF-alpha is responsive to similar or different molecular regulators than those relevant to macrophages. TNF-alpha release from cultured human adipose tissue and isolated adipocytes was examined using an ELISA. Insulin, cortisol or the thiazolidinedione, BRL 49653, did not have a significant effect on TNF-alpha release from adipose tissue or isolated adipocytes. In contrast, lipopolysaccharide (LPS), a major stimulus of TNF-alpha protein production in monocytes and macrophages, resulted in a fivefold stimulation of TNF-alpha release from human adipose tissue. Significant stimulation of TNF-alpha release was also seen from isolated adipocytes, indicating that the increase in TNF-alpha release from adipose tissue in the presence of LPS is unlikely to be entirely attributable to contaminating monocytes or macrophages. Consistent with this observation was the finding that mRNA for CD14, a known cellular receptor for LPS, is expressed in human adipocytes. The increase in TNF-alpha protein release in response to LPS was blocked by an inhibitor of the matrix metalloproteinase responsible for the cleavage of the membrane-bound proform of TNF-alpha, indicating that this release represented regulated secretion and was not due to cell lysis. In conclusion, the regulation of TNF-alpha protein release from human adipose tissue and isolated adipocytes appears to be similar to its regulation in cell types more traditionally implicated in host defence. The production by the adipocyte of a range of molecules involved in host defence-TNF-alpha, factors D, B and C3, interleukin-6, and macrophage colony-stimulating factor--suggest that this cell type may make a significant contribution to innate immunity.

scholarly journals Increased adipose tissue secretion of interleukin-6, but not of leptin, plasminogen activator inhibitor-1 or tumour necrosis factor alpha, in Graves' hyperthyroidism

2002 ◽  
pp. 607-611 ◽  
Author(s):  
H Wahrenberg ◽  
A Wennlund ◽  
J Hoffstedt
Keyword(s):  
Adipose Tissue ◽  
Plasminogen Activator Inhibitor ◽  
Tumour Necrosis Factor Alpha ◽  
Tnf Alpha ◽  
Plasminogen Activator Inhibitor 1 ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Activator Inhibitor ◽  
Necrosis Factor ◽  
Pai 1

OBJECTIVE: This study was designed to investigate adipose tissue secretion of interleukin-6 (IL-6), leptin, tumour necrosis factor alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) in Graves' hyperthyroidism. DESIGN: We studied 10 patients before and during (after 8 weeks) anti-thyroid treatment for Graves' hyperthyroidism and 16 healthy, euthyroid control subjects. METHODS: Plasma levels of thyroid hormones and serum/plasma levels of IL-6, leptin, TNF-alpha and PAI-1 were analysed. Subcutaneous fat biopsies were taken for subsequent measurement of IL-6, leptin, TNF-alpha and PAI-1 protein secretion. RESULTS: In patients with Graves' disease, the anti-thyroid treatment resulted in significant reductions of plasma thyroxine and triiodothyronine levels. No differences in serum concentration or adipose tissue secretion of leptin or TNF-alpha were observed either before, as compared with during, anti-thyroid treatment, or in comparison with euthyroid controls. In contrast, plasma PAI-1 activity, but not adipose tissue secretion of PAI-1, was increased both in Graves' disease before as compared with during anti-thyroid treatment (P=0.01) and in thyrotoxic patients compared with euthyroid controls (P=0.0001). Finally, adipose secretion of IL-6 was increased both before (8-fold, P=0.001) and during (6-fold, P<0.0001) treatment as compared with control subjects. Accordingly, serum concentration of IL-6 was also increased by about 50% in thyrotoxic patients as compared with healthy controls (P=0.03). CONCLUSIONS: In Graves' hyperthyroidism regardless of thyroid status, adipose tissue secretion of IL-6, but not of leptin, TNF-alpha or PAI-1, is markedly increased in comparison with euthyroid controls. This suggests that autoimmune thyroidal disorder may regulate adipose tissue release of IL-6.

scholarly journals Tumour necrosis factor-alpha stimulates increased expression of prostaglandin endoperoxide H synthase Type 2 mRNA in amnion-derived WISH cells

1998 ◽  
Vol 20 (2) ◽  
pp. 221-231 ◽  
Author(s):  
WR Hansen ◽  
T Sato ◽  
MD Mitchell
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Early Gene ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Prostaglandin Endoperoxide ◽  
Factor Alpha ◽  
Endoperoxide H Synthase ◽  
Necrosis Factor

We have evaluated the mechanism by which tumour necrosis factor-alpha (TNF-alpha) induces increased prostaglandin (PG) biosynthesis in amnion-derived WISH cells. WISH cells were treated with 50 ng/ml TNF-alpha or vehicle for 0-24 h. PGE2 production was stimulated by TNF-alpha within 2 h and continued to accumulate for at least 24 h. Increased prostaglandin endoperoxide H synthase (PGHS)-2 mRNA expression was evident within 30 min and was highest by 1 h, returning to unstimulated levels by 2 h. The PGHS-2 mRNA was re-induced at 8 h and was also elevated at 16 h. Immunoreactive PGHS-2 protein was nearly undetectable in control cells. However, within 30 min of TNF-alpha treatment, PGHS-2 protein was elevated and was induced for at least 16 h suggesting rapid production of both the PGHS-2 mRNA and protein. Transcription run-on assays indicated that the initial increase in the PGHS-2 mRNA was due to a 20-fold increase in the rate of transcription. The PGHS-2 mRNA decayed with an apparent half-life of 1 h in TNF-alpha-stimulated WISH cells. Induction of PGHS-2 expression proceeded in the presence of 10 microg/ml cycloheximide which agrees with the classification of PGHS-2 as an immediate early gene. These results indicate that a bi-phasic induction of the PGHS-2 mRNA is due, in part, to an initial transcriptional activation which results in rapid and continued synthesis of the PGHS-2 protein. This may be a unique characteristic of amnion cells which may be partially responsible for increased PG concentrations in the amniotic fluid during infection-associated preterm labour.

scholarly journals Increased TNF-alpha expression in cultured mouse embryos exposed to teratogenic concentrations of glucose

Reproduction ◽  
2003 ◽  
pp. 527-534 ◽  
Author(s):  
A Torchinsky ◽  
I Brokhman ◽  
J Shepshelovich ◽  
H Orenstein ◽  
S Savion ◽  
...  
Keyword(s):  
Neural Tube ◽  
Tumour Necrosis Factor Alpha ◽  
Mouse Embryos ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
High Concentrations ◽  
Necrosis Factor ◽  
Active Caspase ◽  
Embryonic Death

Diabetes-induced early embryonic death is accompanied by an increased expression of tumour necrosis factor alpha (TNF-alpha) in the embryonic microenvironment. The aim of the present study was to evaluate whether diabetes-induced embryopathic stress may also alter the expression of TNF-alpha produced by the embryo itself. As a model, whole postimplantation embryos were cultured for 24 h in a medium with high concentrations of glucose, one of the main diabetes-associated teratogenic metabolites. An anomaly such as an open neural tube was used as an end-point characterizing the glucose-induced teratogenic effect and the number of somites was counted to evaluate growth retardation induced by glucose. The expression of TNF-alpha (by immunohistochemistry), apoptosis (by TdT-mediated dUTP nick-end labelling; TUNEL) and the activity of caspases 3 and 8 (by a fluorometric assay) were evaluated in normal and malformed embryos. Ninety-seven per cent of the embryos exposed to 1300 mg glucose dl(-1) exhibited an open neural tube. The percentage of malformed embryos was smaller in media containing 800 and 500 mg glucose dl(-1) (68 and 37%, respectively) but it still exceeded significantly the value registered in embryos developing in a normoglycaemic medium (12%). In addition, a significant decrease in the number of somites was observed in embryos developing in media containing 1300 and 800 mg glucose dl(-1). Malformed embryos exhibited a greater number of nuclei that were positive in the TUNEL assay as well as a higher amount of active caspase 8 compared with normal embryos (with closed neural folds). TNF-alpha expression was detected in the neuroepithelial layer of the neural tube of the malformed embryos, whereas the expression of this cytokine was weak, if detectable, in normal embryos. Together, these findings indicate that TNF-alpha produced by the embryo may be involved in regulating the response of embryos to diabetes-generated embryopathic stress.

scholarly journals Bifunctional effects of tumor necrosis factor alpha (TNF alpha) on the growth of mature and primitive human hematopoietic progenitor cells: involvement of p55 and p75 TNF receptors

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3152-3159 ◽  
Author(s):  
LS Rusten ◽  
FW Jacobsen ◽  
W Lesslauer ◽  
H Loetscher ◽  
EB Smeland ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Colony Growth ◽  
Tnf Alpha ◽  
Tnf Receptors ◽  
Hematopoietic Progenitor ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Factor Alpha ◽  
Necrosis Factor ◽  
Stimulation Of

Abstract Tumor necrosis factor alpha (TNF alpha) has previously been reported to have both inhibitory and stimulatory effects on hematopoietic progenitor cells. Specifically, TNF alpha has been proposed to stimulate early hematopoiesis in humans. In the present study we show that TNF alpha, in a dose-dependent fashion, can potently inhibit the growth of primitive high proliferative potential colony-forming cells (HPP-CFCs) stimulated by multiple cytokine combinations. Using agonistic antibodies to the p55 and p75 TNF receptors or TNF alpha mutants specific for either of the two TNF receptors, we show that both receptors can mediate this inhibition. In contrast, the potent stimulation of interleukin-3 (IL-3) plus granulocyte-macrophage colony- stimulating factor (GM-CSF) induced HPP-CFC colony formation observed at low concentrations of TNF alpha (2 ng/mL) was only a p55-mediated event. Moreover, the stimulatory effects of TNF alpha on GM-CSF or IL-3- induced colony formation, as well as the inhibition of G-CSF-induced colony growth, were also exclusively signaled through the p55 TNF receptor. Taken together, our results suggest that the inhibitory effects of TNF alpha on primitive bone marrow progenitor cells are mediated through both p55 and p75 TNF receptors, whereas the p55 receptor exclusively mediates the bidirectional effects on more mature, single factor-responsive bone marrow progenitor cells as well as stimulation of IL-3 plus GM-CSF-induced HPP-CFC colony growth.

scholarly journals Effect of Exercise Training on Interleukin-6, Tumour Necrosis Factor Alpha and Functional Capacity in Heart Failure

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Neil A. Smart ◽  
Alf I. Larsen ◽  
John P. Le Maitre ◽  
Almir S. Ferraz
Keyword(s):  
Exercise Training ◽  
Tumour Necrosis Factor ◽  
Interleukin 6 ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Alpha ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Cytokine Levels ◽  
Factor Alpha ◽  
Necrosis Factor

Background. We pooled data from four studies, to establish whether exercise training programs were able to modulate systemic cytokine levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). A second aim was to establish if differences in ExT regimens are related to degree of change in cytokines and peak VO2.Methods. Data from four centres relating to training protocol, exercise capacity, and cytokine measures (TNF-alpha and IL-6) were pooled for analysis.Results. Data for 106 CHF patients were collated (98 men, age 62 ± 10 yrs, wt 79 ± 14 Kg). Patients were moderately impaired (peak VO216.9 ± 4.4 mls/kg/min), with moderate LV systolic dysfunction (EF 30 ± 6.9%), 78% (83) had ischaemic cardiomyopathy. After ExT, peak VO2increased 1.4 ± 3.4 ml/kg/min (P<.001), serum TNF-alpha decreased 1.9 ± 8.6 pg/ml (P=.02) and IL-6 was not significantly changed (0.5 ± 5.4 pg/ml,P=.32) for the whole group. Baseline and post-training peak VO2changes were not correlated with change in cytokine levels.Conclusions. Exercise training reduces levels TNF-alpha but not IL-6 in CHF. However, across a heterogenic patient group, change in peak VO2was not correlated with alterations in cytokine levels. While greater exercise volume (hours) was superior in improving peak VO2, no particular characteristic of ExT regimes appeared superior in effecting change in serum cytokines.

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