Cytotoxicity of IFN-γ and TNF-α for Vascular Endothelial Cell Is Mediated by Nitric Oxide

Yamaoka, Junichi; Kabashima, Kenji; Kawanishi, Michihiro; Toda, Ken‐ichi

doi:10.1006/bbrc.2002.6487

Cited by 60 publications

(42 citation statements)

References 26 publications

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“…The antiangiogenic effect was mainly due to apoptosis of both murine-and tumour-derived endothelial cells, reflecting previous findings in IFN-g-transfected brain tumour cells (Fathallah-Shaykh et al, 2000). The p38 MAPK/Stat1/IRF-1 pathway (Wang et al, 1999;Huang et al, 2002;Lee et al, 2005), cathepsin B (Li and Pober, 2005), Fas/FasL interaction (Li et al, 2002), integrin function (Ruegg et al, 1998) and NO production (Yamaoka et al, 2002;Vekemans et al, 2004;Lee et al, 2005) have been shown to drive IFN-g-dependent apoptosis of endothelial cells. As not only human but also murine endothelial cells in ACN/IFN-g xenografts were TUNEL-positive, neither the released human IFN-g nor other species-specific mediators could be involved in mediating apoptosis in our model.…”

Section: Discussionsupporting

confidence: 82%

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

et al. 2006

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Tumour progression in neuroblastoma (NB) patients correlates with high vascular index. We have previously shown that the ACN NB cell line is tumorigenic and angiogenic in immunodeficient mice, and that interferon-g (IFN-g) gene transfer dampens ACN tumorigenicity. As IFN-g represses lymphocyte-induced tumour angiogenesis in various murine models and inhibits proliferation and migration of human endothelial cells, we have investigated the antiangiogenic activity of tumour-derived IFN-g and the underlying mechanism(s). In addition, we characterised the tumour vasculature of the ACN xenografts, using the chick embryo chorioallantoic membrane assay. We show that the ACN/IFN-g xenografts had a lower microvessel density and less in vivo angiogenic potential than the vector-transfected ACN/neo. The vascular channels of both xenografts were formed by a mixed endothelial cell population of murine and human origin, as assessed by the FICTION (fluorescence immunophenotyping and interphase cytogenetics) technique. With respect to ACN/neo, the ACN/IFN-g xenografts showed more terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling-positive human and murine endothelial cells, suggesting that inhibition of angiogenesis by IFN-g was dependent on the induction of apoptosis, likely mediated by nitric oxide. Once the dual origin of tumour vasculature is confirmed in NB patients, the xenograft model described here will prove useful in testing the efficacy of different antiangiogenic compounds.

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Section: Discussionsupporting

confidence: 82%

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

et al. 2006

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“…Like TDPBi, TNF-α exhibits potent cytotoxicity to vascular endothelial cells, although vascular smooth muscle cells, fibroblasts, and epithelial cells are resistant to cytokine-mediated cytotoxicity. [23][24][25] Although the mechanisms underlying endothelial cell death induced by TNF-α are not simple, it has been shown that nitric oxide 26,27) and the product(s) of aldose reductase catalysis 28) may mediate the cytotoxicity. It remains to be determined whether TDPBi and TNF-α exhibit cytotoxicity to vascular endothelial cells through a common pathway.…”

Section: Discussionmentioning

confidence: 99%

An Organobismuth Compound that Exhibits Selective Cytotoxicity to Vascular Endothelial Cells in Vitro

Fujiwara

Mitani

Yasuike

et al. 2005

JOURNAL OF HEALTH SCIENCE

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Selective cytotoxicity of chemical compounds to vascular endothelial cells is often beneficial for clinical applications including antivascular cancer therapy. In this study, the cytotoxicity of 35 organic compounds containing bismuth or antimony was evaluated based on the leakage of lactate dehydrogenase and morphologic observations in cultured bovine aortic endothelial cells and other cell types. The results indicate that only tris[2-(N,Ndimethylaminomethyl)phenyl]-bismuthane (TDPBi) had potent cytotoxicity to bovine aortic endothelial cells but not to bovine aortic smooth muscle cells and porcine kidney epithelial LLC-PK 1 cells; the compound exhibited moderate cytotoxicity to human fetal lung fibroblastic IMR-90 cells. Neither inorganic bismuth nor tris[2-(N,Ndimethylaminomethyl)phenyl]stibane, in which antimony substitutes for bismuth with the same organic structure as TDPBi, exhibited cytotoxicity to vascular endothelial cells, suggesting that the entire structure of TDPBi is required for selective cytotoxicity. The present data revealed that TDPBi has selective cytotoxicity to vascular endothelial cells, which may be applicable in antivascular cancer therapy.

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“…Oxygen-glucose deprivation induces iNOS expression, thereby increasing concentrations of nitric oxide and peroxynitrites associated with apoptosis [89]. The inflammation-associated increase in TNF-α expression, was accompanied by an increased NO expression in murine vascular EC through an undetermined mechanism [90], and also induced expression of reactive oxygen species through the Rho family GTP binding protein Rac1, and during reperfusion through a pathway incorporating PKC [91,92]. Excitotoxicity induced mitochondrial damage may result in activation of caspase 9, and initiate apoptosis by the The regular pattern of micro-vasculature is also lost in the vicinity of the infarction.…”

Section: Endothelial Cell Apoptosismentioning

confidence: 99%

Gene activation and protein expression following ischaemic stroke: strategies towards neuroprotection

et al. 2005

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Current understanding of the patho-physiological events that follow acute ischaemic stroke suggests that treatment regimens could be improved by manipulation of gene transcription and protein activation, especially in the penumbra region adjacent to the infarct. An immediate reduction in excitotoxicity in response to hypoxia, as well as the subsequent inflammatory response, and beneficial control of reperfusion via collateral revascularization near the ischaemic border, together with greater control over apoptotic cell death, could improve neuronal survival and ultimately patient recovery. Highly significant differences in gene activation between animal models for stroke by middle cerebral artery occlusion, and stroke in patients, may explain why current treatment strategies based on animal models of stroke often fail. We have highlighted the complexities of cellular regulation and demonstrated a requirement for detailed studies examining cell specific protective mechanisms after stroke in humans.

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Cytotoxicity of IFN-γ and TNF-α for Vascular Endothelial Cell Is Mediated by Nitric Oxide

Cited by 60 publications

References 26 publications

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

Angiogenesis in a human neuroblastoma xenograft model: mechanisms and inhibition by tumour-derived interferon-γ

An Organobismuth Compound that Exhibits Selective Cytotoxicity to Vascular Endothelial Cells in Vitro

Gene activation and protein expression following ischaemic stroke: strategies towards neuroprotection

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