Pentoxifylline prevents tumor necrosis factor-induced suppression of endothelial cell surface thrombomodulin

Ohdama, Shinichi; Takano, Shogo; Ohashi, Kazuteru; Miyake, Shuji; Aoki, Nobuo

doi:10.1016/0049-3848(91)90378-a

Cited by 30 publications

(9 citation statements)

References 23 publications

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“…Investigations of the last decade revealed that pentoxifylline, a potential antiinflammatory drug, abolished the effects of TNF-␣ (7,28,37). The accumulation of viral nucleoprotein in the presence of pentoxyfilline (5 mM; Sigma, St. Louis, Mo.)…”

mentioning

confidence: 99%

Effects of Tumor Necrosis Factor Alpha on Sin Nombre Virus Infection In Vitro

Khaiboullina

Netski

Krumpe

et al. 2000

J Virol

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Previous data indicate that immune mechanisms may be involved in developing capillary leakage during Sin Nombre virus (SNV) infection. Therefore, we investigated production of tumor necrosis factor alpha (TNF-␣) by human alveolar macrophages and human umbilical vein endothelial cells (HUVEC) after infection with SNV. In addition, we examined the effect of TNF-␣ on HUVEC monolayer leakage. Our results reveal that although TNF-␣ decreases accumulation of viral nucleoproteins, TNF-␣ levels do not change in SNV-infected cells. In addition, supernatants from SNV-infected human alveolar macrophages did not cause a significant increase in endothelial monolayer permeability.

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mentioning

confidence: 99%

Effects of Tumor Necrosis Factor Alpha on Sin Nombre Virus Infection In Vitro

Khaiboullina

Netski

Krumpe

et al. 2000

J Virol

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“…TM biosynthesis is decreased by tumor necrosis factor (TNF), 6 -15 interleukin-1, 11,16 endotoxin, 17 hypoxia, 18 and transforming growth factor ␤ (TGF␤). 19 Agonists, including retinoic acid, 20 -22 cAMP, 10,11,[23][24][25][26][27][28][29] histamine, 30 forskolin, 23,25 phorbol esters, 11,23,31,32 vascular endothelial growth factor (VEGF), 33 and thrombin, 34 enhance TM transcription in different cell types. Heat shock of vascular endothelial cells induces an upregulatory transcriptional response that abrogates the suppressive effect of TNF.…”

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confidence: 99%

Mutations in Promoter Region of Thrombomodulin and Venous Thromboembolic Disease

Flem

Picard

Emmerich

et al. 1999

ATVB

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Abstract-The present study was designed to analyze the thrombomodulin proximal promoter region spanning nucleotides Ϫ293 to Ϫ12 to search for polymorphisms that could modify thrombomodulin gene expression in patients with venous thromboembolic disease. The study population comprised 205 patients and 394 healthy subjects of similar age and sex distribution. No polymorphisms and only 1 point mutation (G-33A) were found. The G-33A mutation was present at the heterozygous state in 2 patients and in 1 control. Being more frequent in the patients (0.97%) than in the controls (0.25%), the G-33A mutation might be a risk factor for venous thrombosis. To investigate the effect of this mutation on the thrombomodulin promoter activity, the proximal promoter region of the gene (bearing or not bearing the G-33A mutation) was inserted into a promotorless expression vector, upstream of the firefly luciferase gene, and transiently transfected into EA.hy926 endothelial cells. Under the conditions of the assay, the G-33A mutation mildly decreased the promoter activity. This study confirms that abnormalities of the thrombomodulin proximal promoter are not frequent in patients with venous thromboembolism.

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“…Clinical and animal studies show that injury from ionizing radiation is associated with loss of thrombomodulin from endothelium [41]. Also, PTX is shown to increase the levels of thrombomodulin in the endothelium by increasing cAMP [40, 42]. It is conceivable that synergistic radioprotection by the GT3-PTX combination may involve beneficial effects on thrombomodulin levels.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Radioprotection by Gamma-Tocotrienol and Pentoxifylline: Role of cAMP Signaling

et al. 2013

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Purpose. This study was designed to determine the efficacy and mechanisms of radioprotection by the combination of gamma-tocotrienol (GT3) and pentoxifylline (PTX) against acute radiation injury. Materials and Methods. Post-irradiation survival was monitored to determine the most efficacious dose and time of administration of PTX. Dose reduction factor (DRF) was calculated to compare the radioprotective efficacy of the combination. To determine the mechanism of synergistic radioprotection by the combination, mevalonate or calmodulin were coadministered with the GT3-PTX combination. Mevalonate was used to reverse the inhibitory effect of GT3 on 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), and calmodulin was used to reverse the inhibition of phosphodiesterase (PDE) by PTX. Results. The combination was most effective when 200 mg/kg of PTX was administered 15 min before irradiation along with 200 mg/kg of GT3 (−24 h) and resulted in a DRF of 1.5. White blood cells and neutrophil counts showed accelerated recovery in GT3-PTX-treated groups compared to GT3. Mevalonate had no effect on the radioprotection of GT3-PTX; calmodulin abrogated the synergistic radioprotection by GT3-PTX. Conclusion. The mechanism of radioprotection by GT3-PTX may involve PDE inhibition.

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Pentoxifylline prevents tumor necrosis factor-induced suppression of endothelial cell surface thrombomodulin

Cited by 30 publications

References 23 publications

Effects of Tumor Necrosis Factor Alpha on Sin Nombre Virus Infection In Vitro

Effects of Tumor Necrosis Factor Alpha on Sin Nombre Virus Infection In Vitro

Mutations in Promoter Region of Thrombomodulin and Venous Thromboembolic Disease

Synergistic Radioprotection by Gamma-Tocotrienol and Pentoxifylline: Role of cAMP Signaling

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