scholarly journals The role of tumour necrosis factor (TNF)-α resistance in obesity and insulin resistance

Diabetologia ◽  
2000 ◽  
Vol 43 (4) ◽  
pp. 525-525 ◽  
Author(s):  
Not Available Not Available
Keyword(s):  
Insulin Resistance ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Tnf Α ◽  
Necrosis Factor

scholarly journals The tumour necrosis factor-sensitive pool of sphingomyelin is resynthesized in a distinct compartment of the plasma membrane

1998 ◽  
Vol 333 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Nathalie ANDRIEU-ABADIE ◽  
Stéphane CARPENTIER ◽  
Robert SALVAYRE ◽  
Thierry LEVADE
Keyword(s):  
Plasma Membrane ◽  
Golgi Apparatus ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Signal Transduction Pathway ◽  
Recycling Endosomes ◽  
Vesicular Traffic ◽  
Tnf Α ◽  
Necrosis Factor

Sphingomyelin (SM) biosynthesis is believed to occur in the early Golgi apparatus, plasma membrane and recycling endosomes. In the present study, the localization of the SM synthesis that follows its hydrolysis upon activation of the SM signal-transduction pathway was investigated in human skin fibroblasts treated with tumour necrosis factor (TNF) α. After TNFα-induced degradation, the intracellular SM levels returned to baseline levels within 30–60 min in cells treated at 37 °C. Pretreatment or co-incubation of cells with bacterial sphingomyelinase or phospholipase C, decreasing the SM and phosphatidylcholine content in the external leaflet of the plasma membrane respectively, did not inhibit SM resynthesis. However, SM resynthesis was not observed when TNFα-treated cells were continuously exposed to exogenous sphingomyelinase, suggesting that under these particular conditions the resynthesized SM becomes accessible to the enzyme. Furthermore, whereas inhibition of vesicular traffic/endocytosis at 4 °C blocked exoplasmic SM resynthesis, it did not alter SM resynthesis in TNFα-treated fibroblasts, negating the role of endosomes and the Golgi apparatus. This was further evidenced by the finding that after SM resynthesis, TNFα was again able to promote SM turnover, even at 4 °C. In addition, when the exoplasmic leaflet SM was hydrolysed by treating fibroblasts with bacterial sphingomyelinase, resynthesis of SM occurred at 37 °C much more slowly than after TNFα treatment. These findings support strongly the conclusion that the SM, which is resynthesized after TNFα-induced hydrolysis, resides in the cytosolic leaflet of the plasma membrane, and that the process involved in this resynthesis displays characteristics different from those of the previously described SM synthases.

Role of tumour necrosis factor receptor-1 and nuclear factor-κB in production of TNF-α-induced pro-inflammatory microparticles in endothelial cells

2014 ◽  
Vol 112 (09) ◽  
pp. 580-588 ◽  
Author(s):  
Sung Kyul Lee ◽  
Seung-Hee Yang ◽  
Il Kwon ◽  
Ok-Hee Lee ◽  
Ji Hoe Heo
Keyword(s):  
Endothelial Cells ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Nuclear Factor Κb ◽  
Tumour Necrosis Factor Receptor ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Tnf Α ◽  
Necrosis Factor

SummaryTumour necrosis factor-α (TNF-α) is upregulated in many inflammatory diseases and is also a potent agent for microparticle (MP) generation. Here, we describe an essential role of TNF-α in the production of endothelial cell-derived microparticles (EMPs) in vivo and the function of TNF-α-induced EMPs in endothelial cells. We found that TNF-α rapidly increased blood levels of EMPs in mice. Treatment of human umbilical vein endothelial cells (HUVECs) with TNF-α also induced EMP formation in a time-dependent manner. Silencing of TNF receptor (TNFR)-1 or inhibition of the nuclear factor-κB (NF-κB) in HUVECs impaired the production of TNF-α-induced EMP. Incubation of HUVECs with PKH-67-stained EMPs showed that endothelial cells readily engulfed EMPs, and the engulfed TNF-α-induced EMPs promoted the expression of pro-apoptotic molecules and upregulated intercellular adhesion molecule-1 level on the cell surface, which led to monocyte adhesion. Collectively, our findings indicate that the generation of TNF-α-induced EMPs was mediated by TNFR1 or NF-κB and that EMPs can contribute to apoptosis and inflammation of endothelial cells.

scholarly journals Down-regulation of cyclic-nucleotide phosphodiesterase 3B in 3T3-L1 adipocytes induced by tumour necrosis factor α and cAMP

2000 ◽  
Vol 346 (2) ◽  
pp. 337-343 ◽  
Author(s):  
Tova RAHN LANDSTRÖM ◽  
Jie MEI ◽  
Marie KARLSSON ◽  
Vincent MANGANIELLO ◽  
Eva DEGERMAN
Keyword(s):  
Insulin Resistance ◽  
Tumour Necrosis Factor ◽  
Cyclic Nucleotide ◽  
Tumour Necrosis ◽  
Tumour Necrosis Factor Α ◽  
Down Regulation ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

We have used murine 3T3-L1 cells, which differentiate in culture and acquire morphological and biochemical features of mature adipocytes, as a model for studying the expression of cyclic-nucleotide phosphodiesterase (PDE) 3B activity, protein and mRNA during differentiation and during long-term treatment of the cells with tumour necrosis factor α (TNF-α), a cytokine associated with insulin resistance, and a cAMP analogue, N6,2ʹ-O-dibutyryl cAMP (dbcAMP). PDE3B activity, protein and mRNA could be detected 4 days after the initiation of differentiation of 3T3-L1 preadipocytes. Treatment of 3T3-L1 adipocytes with 10 ng/ml TNF-α for 24 h produced a maximal (50%) decrease in PDE3B activity, protein and mRNA, which was well correlated with both activation of protein kinase A (PKA) and stimulation of lipolysis, presumably reflecting an increase in intracellular cAMP concentration. To investigate the effect of cAMP on PDE3B we treated 3T3-L1 adipocytes with dbcAMP. After 4 h with 0.5 mM dbcAMP, PDE3B activity was decreased by 80%, which was also correlated with a decrease in PDE3B protein and mRNA. This effect was abolished in the presence of N-[2-(bromocinnamylamino)ethyl]-5-isoquinolinesulphonamide] (H-89), a specific PKA inhibitor. We conclude that the lipolytic effect of TNF-α involves the down-regulation of PDE3B, which is associated with increased activation of PKA, presumably owing to increased levels of cAMP. In addition, the PKA activation induced by dbcAMP resulted in the down-regulation of PDE3B. These results, which suggest that PDE3B is a novel target for long-term regulation by TNF-α and cAMP, could contribute to the understanding of the mechanisms of insulin resistance.

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