Impaired Induction of Adhesion Molecule Expression in Immortalized Endothelial Cells Leads to Functional Defects in Dynamic Interactions With Lymphocytes

Oostingh, Gertie Janneke; Schlickum, Stephanie; Friedl, Peter; Schön, Michael P.

doi:10.1038/sj.jid.5700828

Cited by 20 publications

(22 citation statements)

References 23 publications

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“…The reason for the differences could be due to the immortalization of the endothelial cells which often results in impairment of induction of adhesion molecules. 33 VCAM-1 was increased by TNF-a in endothelial cells. 34 TNF-a induced E-selectin was not augmented by the addition of paclitaxel.…”

Section: Discussionmentioning

confidence: 98%

Paclitaxel Potentiates Inflammatory Cytokine-induced Prothrombotic Molecules in Endothelial Cells

Wood¹,

Xing²,

Tesfamariam³

2010

Journal of Cardiovascular Pharmacology

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To overcome the limitations of balloon expandible metal stent-induced neointimal smooth muscle cell proliferation, drug-coated stent devices have been developed. Drug eluting stents release high concentrations of antiproliferative agents, such as paclitaxel, to reduce neointimal hyperplasia. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), is known to cause severe endothelial dysfunction and accelerate atherosclerotic lesion progression. The interaction of TNF-alpha and paclitaxel on the release of prothrombotic molecules was examined in endothelial cells. Treatment of endothelial cells with paclitaxel had no direct effect on tissue factor (TF) expression, but TNF-alpha increased TF. Cotreatment of paclitaxel with TNF-alpha markedly augmented the release of TF. TNF-alpha induced release of plasminogen activator inhibitor but no synergism occurred with paclitaxel. Treatment of endothelial cells with paclitaxel and TNF-alpha reduced expression of thrombomodulin and protein C receptor. Tissue factor pathway inhibitor expression was reduced by prolonged treatment with either paclitaxel or TNF-alpha. The adhesion molecule, CD62 E, was induced by TNF-alpha; however, CD31, CD62 P, and CD106 were not affected by paclitaxel and TNF-alpha. Apoptosis was not observed with cotreatment of endothelial cells with paclitaxel and TNF-alpha. CD59-positive microparticles were released in response to TNF-alpha, but the release was not augmented by paclitaxel. Paclitaxel and TNF-alpha increased the nitrotyrosination of proteins. These findings indicate that paclitaxel enhances TNF-alpha-induced release of TF, and downregulated thrombomodulin, increased protein nitration, which may subsequently favor prothrombotic intimal surface.

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Section: Discussionmentioning

confidence: 98%

Paclitaxel Potentiates Inflammatory Cytokine-induced Prothrombotic Molecules in Endothelial Cells

Wood¹,

Xing²,

Tesfamariam³

2010

Journal of Cardiovascular Pharmacology

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“…To address this issue, long-lasting endothelial cells have been generated by using oncogenic factors, including simian virus 40 (SV40) large-T antigen112, polyoma middle-T113 and telomerase reverse transcriptase (TERT)114,115. However, immortalization of endothelial cells by these approaches results in the chronic activation of the MAPK signalling pathway, which leads to the generation of highly proliferative and hypermetabolic endothelial cells that have lost many of their essential angiogenic and/or adhesive features, including impaired responsiveness to angiogenic factors, and the expression of cytokines that are not physiologically expressed by endothelial cells.…”

Section: Models To Study the Vascular Nichementioning

confidence: 99%

Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors

2010

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The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an ‘angiocrine’ mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents.

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“…Gene expression was assessed by reverse transcription-PCR (Oostingh et al, 2007). Primers and reaction conditions are indicated in Supplementary Table S1.…”

Section: Semiquantitative Reverse Transcription-pcrmentioning

confidence: 99%

NF-κB Inhibition through Proteasome Inhibition or IKKβ Blockade Increases the Susceptibility of Melanoma Cells to Cytostatic Treatment through Distinct Pathways

Amschler

Schön

Pletz

et al. 2010

Journal of Investigative Dermatology

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Metastasized melanoma is almost universally resistant to chemotherapy. Given that constitutive or drug-induced upregulation of NF-kappaB activity is associated with this chemoresistance, NF-kappaB inhibition may increase the susceptibility to antitumoral therapy. On the cellular level, two principles of NF-kappaB inhibition, proteasome inhibition by bortezomib and IkappaB kinase-beta (IKKbeta) inhibition by the kinase inhibitor of NF-kappaB-1 (KINK-1), significantly increased the antitumoral efficacy of camptothecin. When combined with camptothecin, either of the two NF-kappaB-inhibiting principles synergistically influenced progression-related in vitro functions, including cell growth, apoptosis, and invasion through an artificial basement membrane. In addition, when C57BL/6 mice were intravenously injected with B16F10 melanoma cells, the combination of cytostatic treatment with either of the NF-kappaB-inhibiting compounds revealed significantly reduced pulmonary metastasis compared to either treatment alone. However, on the molecular level, nuclear translocation of p65, cell cycle analysis, and expression of NF-kappaB-dependent gene products disclosed distinctly different molecular mechanisms, resulting in the same functional effect. That proteasome inhibition and IKKbeta inhibition affect distinct molecular pathways downstream of NF-kappaB, both leading to increased chemosensitivity, is previously unreported. Thus, it is conceivable that switching the two principles of NF-kappaB inhibition, once resistance to one of the agents occurs, will improve future treatment regimens.

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Impaired Induction of Adhesion Molecule Expression in Immortalized Endothelial Cells Leads to Functional Defects in Dynamic Interactions With Lymphocytes

Cited by 20 publications

References 23 publications

Paclitaxel Potentiates Inflammatory Cytokine-induced Prothrombotic Molecules in Endothelial Cells

Paclitaxel Potentiates Inflammatory Cytokine-induced Prothrombotic Molecules in Endothelial Cells

Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors

NF-κB Inhibition through Proteasome Inhibition or IKKβ Blockade Increases the Susceptibility of Melanoma Cells to Cytostatic Treatment through Distinct Pathways

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