Peroxynitrite mediates TNF-α-induced endothelial barrier dysfunction and nitration of actin

2006 ◽  
Vol 290 (4) ◽  
pp. L674-L684 ◽  
Author(s):  
Paul Neumann ◽  
Nancy Gertzberg ◽  
Erin Vaughan ◽  
Joshua Weisbrot ◽  
Renee Woodburn ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Dot Blot ◽  
Endothelial Barrier Dysfunction ◽  
Endothelial Monolayers ◽  
Tnf Α ◽  
Cellular Compartmentalization ◽  
Necrosis Factor

We tested the hypothesis that tumor necrosis factor (TNF)-α induces a peroxynitrite (ONOO−)-dependent increase in permeability of pulmonary microvessel endothelial monolayers (PMEM) that is associated with generation of nitrated β-actin (NO2-β-actin). The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin. β-Actin was extracted from PMEM lysate with a DNase-Sepharose column. The extracted β-actin was quantified in terms of its nitrotyrosine/β-actin ratio with antinitrotyrosine and anti-β-actin antibodies, sequentially, by dot-blot assays. The cellular compartmentalization of NO2-β-actin was displayed by showing confocal localization of nitrotyrosine-immunofluorescence with β-actin-immunofluorescence but not with F-actin fluorescence. Incubation of PMEM with TNF (100 ng/ml) for 0.5 and 4.0 h resulted in increases in permeability to albumin. There was an increase in the nitrotyrosine/β-actin ratio at 0.5 h with minimal association of the NO2-β-actin with F-actin polymers. The TNF-induced increase in the nitrotyrosine/β-actin ratio and permeability were prevented by the anti-ONOO− agent Urate. The data indicate that TNF induces an ONOO−-dependent barrier dysfunction, which is associated with the generation of NO2-β-actin.

Tumor Necrosis Factor-α-Mediated Pulmonary Endothelial Barrier Dysfunction

2005 ◽  
Vol 1 (3) ◽  
pp. 233-246 ◽  
Author(s):  
Daniel Angelini ◽  
Jeffrey Hasday ◽  
Simeon Goldblum ◽  
Douglas Bannerman
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Endothelial Barrier ◽  
Barrier Dysfunction ◽  
Endothelial Barrier Dysfunction ◽  
Necrosis Factor

NAD(P)H oxidase mediates the endothelial barrier dysfunction induced by TNF-α

2004 ◽  
Vol 286 (1) ◽  
pp. L37-L48 ◽  
Author(s):  
Nancy Gertzberg ◽  
Paul Neumann ◽  
Victor Rizzo ◽  
Arnold Johnson
Keyword(s):  
Antisense Oligonucleotide ◽  
Oxygen Species ◽  
Text Generation ◽  
Barrier Dysfunction ◽  
Acetoxymethyl Ester ◽  
Endothelial Barrier Dysfunction ◽  
Endothelial Monolayers ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

We tested the hypothesis that the NAD(P)H oxidase-dependent generation of superoxide anion ([Formula: see text]) mediates tumor necrosis factor-α (TNF)-induced alterations in the permeability of pulmonary microvessel endothelial monolayers (PMEM). The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin. The NAD(P)H oxidase subcomponents p47phoxand p22phoxwere assessed by immunofluorescent microscopy and Western blot. The reactive oxygen species [Formula: see text] was measured by the fluorescence of 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetatedi(acetoxymethyl ester), 5 (and 6)-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate-acetyl ester, and dihydroethidium. TNF treatment (50 ng/ml for 4.0 h) induced 1) p47phoxtranslocation, 2) an increase in p22phoxprotein, 3) increased localization of p47phoxwith p22phox, 4) [Formula: see text] generation, and 5) increased permeability to albumin. p22phoxantisense oligonucleotide prevented the TNF-induced effect on p22phox, p47phox, [Formula: see text], and permeability. The scrambled nonsense oligonucleotide had no effect. The TNF-induced increase in [Formula: see text] and permeability to albumin was also prevented by the [Formula: see text] scavenger Cu-Zn superoxide dismutase (100 U/ml). The results indicate that the activation of NAD(P)H oxidase, via the generation of [Formula: see text], mediates TNF-induced barrier dysfunction in PMEM.

Role of TNF-α in ileum tight junction alteration in mouse model of restraint stress

2008 ◽  
Vol 294 (5) ◽  
pp. G1268-G1280 ◽  
Author(s):  
Emanuela Mazzon ◽  
Salvatore Cuzzocrea
Keyword(s):  
Tumor Necrosis Factor ◽  
Tight Junction ◽  
Restraint Stress ◽  
Tumor Necrosis ◽  
Immobilization Stress ◽  
Tunel Staining ◽  
Barrier Dysfunction ◽  
Tnf Α ◽  
Necrosis Factor

Restraint stress induces permeability changes in the small intestine, but little is known about the role of tumor necrosis factor (TNF)-α in the defects of the TJ function. In the present study, we used tumor necrosis factor-R1 knockout mice (TNF-α-R1KO) to understand the roles of TNF-α on ileum altered permeability function in models of immobilization stress. The genetic TNF-α inhibition significantly reduced the degree of 1) TNF-α production in ileum tissues; 2) the alteration of zonula occludens-1 (ZO-1), claudin-2, claudin-4, claudin-5, and β-catenin (immunohistochemistry); and 3) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-α reduces the tight junction permeability in the ileum tissues associated with immobilization stress, suggesting a possible role of TNF-α on ileum barrier dysfunction.

Tumor necrosis factor-α–dependent expression of phosphodiesterase 2: role in endothelial hyperpermeability

Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3569-3576 ◽  
Author(s):  
Joachim Seybold ◽  
Dirk Thomas ◽  
Martin Witzenrath ◽  
Şengül Boral ◽  
Andreas C. Hocke ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tumor Necrosis Factor ◽  
Barrier Function ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

AbstractThe pleiotropic cytokine tumor necrosis factor-α (TNF-α) and thrombin lead to increased endothelial permeability in sepsis. Numerous studies demonstrated the significance of intracellular cyclic nucleotides for the maintenance of endothelial barrier function. Actions of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are terminated by distinct cyclic nucleotide phosphodiesterases (PDEs). We hypothesized that TNF-α could regulate PDE activity in endothelial cells, thereby impairing endothelial barrier function. In cultured human umbilical vein endothelial cells (HUVECs), we found a dramatic increase of PDE2 activity following TNF-α stimulation, while PDE3 and PDE4 activities remained unchanged. Significant PDE activities other than PDE2, PDE3, and PDE4 were not detected. TNF-α increased PDE2 expression in a p38 mitogen-activated protein kinase (MAPK)–dependent manner. Endothelial barrier function was investigated in HUVECs and in isolated mice lungs. Selective PDE2 up-regulation sensitized HUVECs toward the permeability-increasing agent thrombin. In isolated mice lungs, we demonstrated that PDE2 inhibition was effective in preventing thrombin-induced lung edema, as shown with a reduction in both lung wet-to-dry ratio and albumin flux from the vascular to bronchoalveolar compartment. Our findings suggest that TNF-α–mediated up-regulation of PDE2 may destabilize endothelial barrier function in sepsis. Inhibition of PDE2 is therefore of potential therapeutic interest in sepsis and acute respiratory distress syndrome (ARDS).

Tumor necrosis factor-α causes barrier dysfunction mediated by tyrosine198 and tyrosine218 in β-actin

2007 ◽  
Vol 293 (5) ◽  
pp. L1219-L1229 ◽  
Author(s):  
Nancy Gertzberg ◽  
Tina Gurnani ◽  
Paul Neumann ◽  
Anne-Kay Forbes ◽  
Natacha Jean-Louis ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Yellow Fluorescent Protein ◽  
Wild Type ◽  
Barrier Dysfunction ◽  
Junction Protein ◽  
Factor Α ◽  
Cellular Compartmentalization ◽  
Necrosis Factor

We tested the hypothesis that tumor necrosis factor-α (TNF) induces barrier dysfunction of pulmonary microvessel endothelial monolayers (PMEM) mediated by specific tyrosine residues in β-actin. PMEM were transfected with a wild-type, mutant [tyrosine198 to phenylalanine198 (Y198F)], mutant Y218F, or mutant Y306F β-actin construct tagged with enhanced yellow fluorescent protein (EYFP-β-actin). The cellular compartmentalization of wild-type and mutant EYFP-β-actin was displayed using EYFP fluorescence of the tagged β-actin. β-Actin was quantified for the EYFP-tagged and native β-actin using Western blot assay. The effect of the EYFP-β-actin on a cell junction protein was assessed by association of EYFP-β-actin with β-catenin using confocal microscopy and coimmunoprecipitation. The permeability of PMEM was assessed by the clearance rate of Evans blue-labeled albumin. The cellular compartmentalization of wild-type and mutant EYFP-β-actin was similar to the native β-actin. Incubation of PMEM with TNF (100 ng/ml) for 0.5 h resulted in increases in permeability to albumin and a decrease in association of the EYFP-β-actin with β-catenin. However, the expression of the EYFP-Y198F β-actin and EYFP-Y218F β-actin prevented the effect of TNF on β-catenin and barrier function. The vehicle, wild-type EYFP-β-actin, and mutant Y306F β-actin had no affect on the response to TNF. The data indicate that TNF induces an increase in endothelial permeability that is dependent on tyrosine198 and tyrosine218 in β-actin.

#50 Gestational exposure of tumor necrosis factor-α (TNF-α) inhibitor drugs

2019 ◽  
Vol 88 ◽  
pp. 149-150 ◽  
Author(s):  
Erkoseoglu Ilknur ◽  
Kadioglu Mine ◽  
Cavusoglu Irem ◽  
Sisman Mulkiye ◽  
Aran Turhan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Gestational Exposure ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Association of tumor necrosis factor-alpha -308 G/A and -238 G/A polymorphism with diabetic retinopathy: a systematic review and updated meta-analysis.

2020 ◽  
Author(s):  
Wenna Gao ◽  
Ruilin Zhu ◽  
liu yang
Keyword(s):  
Diabetic Retinopathy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Meta Analysis ◽  
Entire Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background: Mounting evidence has suggested tumor necrosis factor-alpha (TNF-α) can promote the development of diabetic retinopathy (DR), and TNF-α gene variants may influence DR risk. However, the results are quite different. Objectives: To comprehensively address this issue, we performed the meta-analysis to evaluate the association of TNF-α-308 G/A and -238 G/A polymorphism with DR. Method: Data were retrieved in a systematic manner and analyzed using STATA Statistical Software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Allelic and genotypic comparisons between cases and controls were evaluated. Results: For the TNF-α-308 G/A polymorphism, overall analysis suggested a marginal association with DR [the OR(95%CI) of (GA versus GG), (GA + AA) versus GG, and (A versus G) are 1.21(1.04, 1.41), 1.20(1.03, 1.39), and 1.14(1.01, 1.30), respectively]. And the subgroup analysis indicated an enhanced association among the European population. For the TNF-α-238 G/A polymorphism, there was mild correlation in the entire group [the OR(95%CI) of (GA versus GG) is 1.55(1.14,2.11) ], which was strengthened among the Asian population. Conclusion: The meta-analysis suggested that -308 A and -238 A allele in TNF-α gene potentially increased DR risk and showed a discrepancy in different ethnicities.

scholarly journals Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis

2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098465
Author(s):  
Like Qian ◽  
Xi Yin ◽  
Jiahao Ji ◽  
Zhengli Chen ◽  
He Fang ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Tumor Necrosis ◽  
Alveolar Epithelial Cell ◽  
Weight Ratio ◽  
B Cell Lymphoma ◽  
Alveolar Epithelial ◽  
Tnf Α ◽  
Necrosis Factor

Background The role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear. Methods Sixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups. Results The wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. Conclusion TNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.

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