Tumor necrosis factor-α and lipopolysaccharide induce apoptotic cell death in bovine glomerular endothelial cells

Meßmer, Udo K.; Briner, Verena; Pfeilschifter, Josef

doi:10.1046/j.1523-1755.1999.00473.x

Cited by 136 publications

(112 citation statements)

References 35 publications

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“…It has been reported for various cell types that glucocorticoids like dexamethasone or hydrocortisone are capable of reducing the level of apoptosis when it is initiated by cytokines or serum-depletion (Wen et al, 1997;Messmer et al, 1999;Huang and Cidlowski, 1999). Thus, we addressed whether hydrocortisone when applied in physiological concentrations can retard the apoptosis-induced impedance decrease that we observed for PBCEC in our system.…”

Section: Resultsmentioning

confidence: 89%

Bioelectrical impedance assay to monitor changes in cell shape during apoptosis

Arndt

Seebach

Psathaki

et al. 2004

Biosensors and Bioelectronics

293

197

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Apoptosis is a strictly regulated and genetically encoded cell 'suicide' that may be triggered by cytokines, depletion of growth factors or certain chemicals. It is morphologically characterized by severe alterations in cell shape like cell shrinkage and disintegration of cell-cell contacts. We applied a non-invasive electrochemical technique referred to as electric cell-substrate impedance sensing (ECIS) in order to monitor the apoptosis-induced changes in cell shape in an integral and quantitative fashion with a time resolution in the order of minutes. In ECIS the cells are grown directly on the surface of small gold-film electrodes (d = 2 mm). From readings of the electrical impedance of the cell-covered electrode, performed with non-invasive, low amplitude sensing voltages, it is possible to deduce alterations in cell-cell and cell-substrate contacts. To improve the sensitivity of this impedance assay we used endothelial cells derived from cerebral micro-vessels as cellular model systems since these are well known to express electrically tight intercellular junctions. Apoptosis was induced by cycloheximide (CHX) and verified by biochemical and cytological assays. The time course of cell shape changes was followed with unprecedented time resolution by impedance readings at 1 kHz and correlated with biochemical parameters. From impedance readings along a broad frequency range of 1-10 6 Hz we could assign the observed impedance changes to alterations on the subcellular level. We observed that disassembly of barrier-forming tight junctions precedes changes in cell-substrate contacts and correlates strongly with the time course of protease activation.

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Section: Resultsmentioning

confidence: 89%

Bioelectrical impedance assay to monitor changes in cell shape during apoptosis

Arndt

Seebach

Psathaki

et al. 2004

Biosensors and Bioelectronics

293

197

View full text Add to dashboard Cite

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“…However, it is also clear that LPS has direct effects on the endothelium (53)(54)(55)(56)(57). As with TNF, in most studies LPS does not induce significant death of human endothelial cells unless new gene expression is blocked (3,6).…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Signals an Endothelial Apoptosis Pathway Through TNF Receptor-Associated Factor 6-Mediated Activation of c-Jun NH2-Terminal Kinase

Hull

McLean

Wong

et al. 2002

The Journal of Immunology

101

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Inflammatory mediators such as TNF and bacterial LPS do not cause significant apoptosis of endothelial cells unless the expression of cytoprotective genes is blocked. In the case of TNF, the transcription factor NF-κB conveys an important survival signal. In contrast, even though LPS can also activate NF-κB, this signal is dispensable for LPS-inducible cytoprotective activity. LPS intracellular signals are transmitted through a member of the Toll-like receptor family, TLR4. This family of receptors transduces signals through a downstream molecule, TNFR-associated factor 6 (TRAF6). In this study, we demonstrate that the C-terminal fragment of TRAF6 (TRAF6-C) inhibits LPS-induced NF-κB nuclear translocation and c-Jun NH2-terminal kinase (JNK) activation in endothelial cells. In contrast, LPS activation of p38 kinase is not inhibited by TRAF6-C. TRAF6-C also inhibits LPS-initiated endothelial apoptosis, but potentiates TNF-induced apoptosis. LPS-induced loss of mitochondrial transmembrane potential, cytochrome c release, and caspase activation are all blocked by TRAF6-C. We demonstrate that TRAF6 signals apoptosis via JNK activation, since inhibition of JNK activation using a dominant-negative mutant also inhibits apoptosis. JNK inhibition blocks caspase activation, but the reverse is not true. Hence, JNK activation lies upstream of caspase activation in response to LPS stimulation.

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“…The toxic effects of DMXAA in WT mice are consistent with changes to normal vascular endothelium causing reduced peripheral blood flow and oedema. Possible mechanisms include TNF-induced increases in vascular permeability (Royall et al, 1989) and TNFinduced apoptosis of normal endothelial cells, which has been observed both in vitro and in vivo (Polunovsky et al, 1994;Messmer et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…The results support the concept that the late, tumour-specific vascular response in WT mice treated at this dose is TNF-dependent. TNF may increase vascular permeability (Royall et al, 1989) as well as induce endothelial cell apoptosis (Polunovsky et al, 1994;Messmer et al, 1999), possibly mediated by reduced avb3 integrin-mediated tumour endothelial cell adhesion (Ruegg et al, 1998). A higher dose of DMXAA does induce tumour regressions in TNFR1 7/7 mice ( Table 2) and although time courses for 5HIAA production at higher doses have not been carried out, the dose response measured after 24 h increases markedly ( Figure 2C), consistent with the generation of a sustained 5HIAA response in TNFR1 7/7 mice at high dose.…”

Section: Experimental Therapeuticsmentioning

confidence: 99%

The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice

Zhao

Kestell

et al. 2002

Br J Cancer

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5,6-dimethylxanthenone-4-acetic acid, a novel antivascular anticancer drug, has completed Phase I clinical trial. Its actions in mice include tumour necrosis factor induction, serotonin release, tumour blood flow inhibition, and the induction of tumour haemorrhagic necrosis and regression. We have used mice with a targeted disruption of the tumour necrosis factor receptor-1 gene as recipients for the colon 38 carcinoma to determine the role of tumour necrosis factor signalling in the action of 5,6-dimethylxanthenone-4-acetic acid. The pharmacokinetics of 5,6-dimethylxanthenone-4-acetic acid, as well as the degree of induced plasma and tissue tumour necrosis factor, were similar in tumour necrosis factor receptor-1 7/7 and wild-type mice. However, the maximum tolerated dose of 5,6-dimethylxanthenone-4-acetic acid was considerably higher in tumour necrosis factor receptor-1 7/7 mice (4100 mg kg 71 ) than in wild-type mice (27.5 mg kg 71 ). The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (25 mg kg 71 ) was strongly attenuated in tumour necrosis factor receptor-1 7/7 mice. However, the reduced toxicity in tumour necrosis factor receptor-1 7/7 mice allowed the demonstration that at a higher dose (50 mg kg 71 ), 5,6-dimethylxanthenone-4-acetic acid was curative and comparable in effect to that of a lower dose (25 mg kg 71 ) in wild-type mice. The 5,6-dimethylxanthenone-4-acetic acid -induced rise in plasma 5-hydroxyindoleacetic acid, used to reflect serotonin production in a vascular response, was larger in colon 38 tumour bearing than in non-tumour bearing tumour necrosis factor receptor-1 7/7 mice, but in each case the response was smaller than the corresponding response in wild-type mice. The results suggest an important role for tumour necrosis factor in mediating both the host toxicity and antitumour activity of 5,6-dimethylxanthenone-4-acetic acid, but also suggest that tumour necrosis factor can be replaced by other vasoactive factors in its antitumour action, an observation of relevance to current clinical studies.

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Tumor necrosis factor-α and lipopolysaccharide induce apoptotic cell death in bovine glomerular endothelial cells

Abstract: Both bacterial LPS and TNF-alpha potently induced apoptotic cell death in glomerular endothelial cells. Direct endotoxin-induced apoptosis may therefore be relevant in the progression of acute renal failure, which is a frequent complication of gram-negative sepsis.

Cited by 136 publications

References 35 publications

Bioelectrical impedance assay to monitor changes in cell shape during apoptosis

Bioelectrical impedance assay to monitor changes in cell shape during apoptosis

Lipopolysaccharide Signals an Endothelial Apoptosis Pathway Through TNF Receptor-Associated Factor 6-Mediated Activation of c-Jun NH2-Terminal Kinase

The antitumour activity of 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in TNF receptor-1 knockout mice

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