Binding of pleomorphic adenoma gene-like 2 to the tumor necrosis factor (TNF)-α-responsive region of the NCF2 promoter regulates p67  expression and NADPH oxidase activity. VOLUME 282 (2007) PAGES 17941-17952

Abstract Oxygen-dependent antimicrobial activity of human polymorphonuclear leukocytes (PMNs) relies on the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate oxidants. As the oxidase transfers electrons from NADPH the membrane will depolarize and concomitantly terminate oxidase activity, unless there is charge translocation to compensate. Most experimental data implicate proton channels as the effectors of this charge compensation, although large-conductance Ca2+-activated K+ (BK) channels have been suggested to be essential for normal PMN antimicrobial activity. To test this latter notion, we directly assessed the role of BK channels in phagocyte function, including the NADPH oxidase. PMNs genetically lacking BK channels (BK−/−) had normal intracellular and extracellular NADPH oxidase activity in response to both receptor-independent and phagocytic challenges. Furthermore, NADPH oxidase activity of human PMNs and macrophages was normal after treatment with BK channel inhibitors. Although BK channel inhibitors suppressed endotoxin-mediated tumor necrosis factor-α secretion by bone marrow-derived macrophages (BMDMs), BMDMs of BK−/− and wild-type mice responded identically and exhibited the same ERK, PI3K/Akt, and nuclear factor-κB activation. Based on these data, we conclude that the BK channel is not required for NADPH oxidase activity in PMNs or macrophages or for endotoxin-triggered tumor necrosis factor-α release and signal transduction BMDMs.

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Acute Tumor Necrosis Factor Alpha Signaling via NADPH Oxidase in Microvascular Endothelial Cells: Role of p47phox Phosphorylation and Binding to TRAF4

Molecular and Cellular Biology ◽

10.1128/mcb.25.6.2320-2330.2005 ◽

2005 ◽

Vol 25 (6) ◽

pp. 2320-2330 ◽

Cited By ~ 148

Author(s):

Jian-Mei Li ◽

Lampson M. Fan ◽

Michael R. Christie ◽

Ajay M. Shah

Keyword(s):

Endothelial Cells ◽

Tumor Necrosis Factor ◽

Nadph Oxidase ◽

Tumor Necrosis ◽

Fold Increase ◽

Microvascular Endothelial Cells ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

ABSTRACT Tumor necrosis factor alpha (TNF-α) receptor-associated factors (TRAFs) play important roles in TNF-α signaling by interacting with downstream signaling molecules, e.g., mitogen-activated protein kinases (MAPKs). However, TNF-α also signals through reactive oxygen species (ROS)-dependent pathways. The interrelationship between these pathways is unclear; however, a recent study suggested that TRAF4 could bind to the NADPH oxidase subunit p47phox. Here, we investigated the potential interaction between p47phox phosphorylation and TRAF4 binding and their relative roles in acute TNF-α signaling. Exposure of human microvascular endothelial cells (HMEC-1) to TNF-α (100 U/ml; 1 to 60 min) induced rapid (within 5 min) p47phox phosphorylation. This was paralleled by a 2.7- ± 0.5-fold increase in p47phox-TRAF4 association, membrane translocation of p47phox-TRAF4, a 2.3- ± 0.4-fold increase in p47phox-p22phox complex formation, and a 3.2- ± 0.2-fold increase in NADPH-dependent O2 − production (all P < 0.05). TRAF4-p47phox binding was accompanied by a progressive increase in extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38MAPK activation, which was inhibited by an O2 − scavenger, tiron. TRAF4 predominantly bound the phosphorylated form of p47phox, in a protein kinase C-dependent process. Knockdown of TRAF4 expression using siRNA had no effect on p47phox phosphorylation or binding to p22phox but inhibited TNF-α-induced ERK1/2 activation. In coronary microvascular EC from p47phox−/− mice, TNF-α-induced NADPH oxidase activation, ERK1/2 activation, and cell surface intercellular adhesion molecule 1 (ICAM-1) expression were all inhibited. Thus, both p47phox phosphorylation and TRAF4 are required for acute TNF-α signaling. The increased binding between p47phox and TRAF4 that occurs after p47phox phosphorylation could serve to spatially confine ROS generation from NADPH oxidase and subsequent MAPK activation and cell surface ICAM-1 expression in EC.

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

Reproductive Toxicology ◽

10.1016/j.reprotox.2019.05.068 ◽

2019 ◽

Vol 88 ◽

pp. 149-150 ◽

Cited By ~ 1

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

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Regulation of BDNF expression in trigeminal ganglion neurons by tumor necrosis factor alpha (TNF-α) depends on neuronal activity

Pharmacological Reports ◽

10.1016/s1734-1140(10)71183-x ◽

2010 ◽

Vol 62 ◽

pp. 74

Author(s):

Ewa Bałkowiec-lskra ◽

Anke Vermehren-Schmaedick ◽

Agnieszka Bałkowiec

Keyword(s):

Tumor Necrosis Factor ◽

Neuronal Activity ◽

Tumor Necrosis ◽

Bdnf Expression ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Trigeminal Ganglion Neurons ◽

Ganglion Neurons ◽

Necrosis Factor

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

Ophthalmic Research ◽

10.1159/000513586 ◽

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.

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

Journal of International Medical Research ◽

10.1177/0300060520984652 ◽

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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Tumor Necrosis Factor-α Production-Enhancing Properties of Novel Adamantylalkylthio Derivatives of Some Heterocyclic Compounds

Zeitschrift für Naturforschung B ◽

10.1515/znb-2005-0419 ◽

2005 ◽

Vol 60 (4) ◽

pp. 471-475 ◽

Cited By ~ 2

Author(s):

Barbara Orzeszko ◽

Tomasz Świtaj ◽

Anna B. Jakubowska-Mućka ◽

Witold Lasek ◽

Andrzej Orzeszko ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Heterocyclic Compounds ◽

Tumor Necrosis ◽

The Novel ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Factor Α ◽

Derivatives Of ◽

Necrosis Factor

Certain adamantylated heterocycles were previously shown to enhance the secretion of tumor necrosis factor alpha (TNF-α) by murine melanoma cells that have been transduced with the gene for human TNF-α and constitutively expressed this cytokine. The stimulatory potency of those compounds depended, among other factors, on the structure of the linker between the adamantyl residue and the heterocyclic core. In the present study, a series of (1-adamantyl)alkylsulfanyl derivatives of heterocyclic compounds was prepared by alkylation of the corresponding thioheterocyles. Of the novel adamantylalkylthio compounds tested in the aforementioned cell line, 2-(2-adamantan-1-ylethylsulfanyl)- 4-methyl-pyrimidine was found to be the most active

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Efficacy of Alpinumisoflavone Isolated from Maclura tricuspidata Fruit in Tumor Necrosis Factor-α-Induced Damage of Human Dermal Fibroblasts

Antioxidants ◽

10.3390/antiox10040514 ◽

2021 ◽

Vol 10 (4) ◽

pp. 514

Author(s):

Sullim Lee ◽

Giang Do Hoang ◽

Daeyoung Kim ◽

Ho Sueb Song ◽

Sungyoul Choi ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Dermal Fibroblasts ◽

The Body ◽

Hazardous Substances ◽

Human Dermal Fibroblasts ◽

Cutaneous Lesions ◽

Matrix Metalloproteinase 1 ◽

Tnf Α ◽

Necrosis Factor

The skin is an important organ in the human body that protects the body from environmentally hazardous substances. Reactive oxygen species (ROS) cause inflammatory reactions and degradation of the extracellular matrix leading to skin aging and various cutaneous lesions. This study evaluated the potential of isoflavones isolated from Maclura tricuspidata fruit to prevent TNF-α-induced skin inflammation in normal human dermal fibroblasts (HDFs). It focused on alpinumisoflavone (AIF) that suppressed the accumulation of ROS and nitric oxide (NO) in tumor necrosis factor-alpha (TNF-α)-treated HDFs. AIF inhibited the TNF-α-induced increase in matrix metalloproteinase-1, decreased procollagen I α1, and suppressed pro-inflammatory mediators and pro-inflammatory cytokines, including NO synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and IL-8 that trigger inflammatory responses. AIF inhibited nuclear factor-κB and activating protein 1 mitogen-activated protein kinases that were increased by TNF-α stimulation. These results suggest that AIF may protect skin from aging and various cutaneous lesions.

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