Tumor necrosis factor alpha (TNF-α) blockade improves natural killer cell (NK) activation, hypertension, and mitochondrial oxidative stress in a preclinical rat model of preeclampsia

ABSTRACT Increased production of tumor necrosis factor alpha (TNF-α) appears to play an important role in the progression of human immunodeficiency virus disease. One treatment strategy being explored is the use of TNF-α inhibitors. TNF-α also appears to be important in conferring resistance to infections, and the inhibition of this cytokine may exacerbate the emergence of opportunistic pathogens, such as Mycobacterium avium complex (MAC). The present study examines the possibility that inhibition of TNF-α will increase the progression of disease in mice infected with MAC. C57BL/6 beige (bg/bg) mice have been shown to be highly susceptible to infection with MAC and are routinely used for testing of antimycobacterial drugs. However, bg/bg mice are known to exhibit impaired phagocyte and natural killer cell function. Since these cell types are important sources of TNF-α, the susceptibility of the bg/bg strain to infection with MAC was compared with those of the heterozygous (bg/+) and wild-type (+/+) strains of C57BL/6 mice. The susceptibilities of the bg/bgand bg/+ strains of mice infected with MAC were found to be comparable. The +/+ strain was the least susceptible. Mycobacterial burden and serum TNF-α levels increased over time in all the strains of mice tested. The bg/+ strain of C57BL/6 mice was then chosen to measure the activity of TNF-α antagonists. Treatment with dexamethasone decreased serum TNF-α levels and increased mycobacterial burden. Treatment with anti-TNF-α antibody or pentoxifylline did not significantly alter serum TNF-α levels but increased mycobacterial burden. Treatment with thalidomide neither consistently altered mycobacterial burden in the spleens or livers of infected mice nor affected serum TNF-α levels.

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Exposure to prolonged unpredictable light impairs spatial memory via induction of oxidative stress and tumor necrosis factor-alpha in rats

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0160 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Oluwaseun S. Faborode ◽

Issa O. Yusuf ◽

Paschal O. Okpe ◽

Ann O. Okudaje ◽

Samuel A. Onasanwo

Keyword(s):

Oxidative Stress ◽

Object Recognition ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Light Exposure ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

Abstract Objectives The human body physiology rapidly changes and adapt to several environmental stimuli, including light. Abnormal artificial light exposures have been shown to affect sleep cycle, cognition, and mood. Although studies have reported inconsistent effects of short-term or constant long-term light exposures, human exposures to artificial lights occur at varying, unpredictable times and duration daily. Here, we studied the effects of long-term unpredictable light exposure on learning, memory, oxidative status, and associated cytokines in rats. Methods Artificial lighting was provided using an array of white light-emitting diodes coupled to a microcontroller that switches them on or off at unpredictable times and duration (light intensity = 200 ± 20 lx). Within the last eight days of 40 days exposure, animals were subjected to open field test, Morris water maze, and novel object recognition behavioral paradigms. Brain levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, reduced glutathione (GSH), glutathione S-transferase (GST), tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF) were assayed. Results Exposed rats showed impaired spatial learning and memory (p<0.05), but no changes in object recognition memory or locomotor activity. Oxidative stress analyses also revealed significant changes in the concentrations of MDA, SOD, catalase, and GSH levels (p<0.05), not GST. Similarly, there was an increased TNF-α expression (p<0.05), not VEGF. Conclusions We conclude that oxidative stress is involved in memory impairment in rats exposed to prolonged unpredictable lights, which again suggests the detrimental effects of extended light exposure on the nervous system.

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Vitamin C Mitigates Oxidative Stress and Tumor Necrosis Factor-Alpha in Severe Community-Acquired Pneumonia and LPS-Induced Macrophages

Mediators of Inflammation ◽

10.1155/2014/426740 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 27

Author(s):

Yuanyuan Chen ◽

Guangyan Luo ◽

Jiao Yuan ◽

Yuanyuan Wang ◽

Xiaoqiong Yang ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Tumor Necrosis Factor ◽

Vitamin C ◽

Tumor Necrosis ◽

Community Acquired Pneumonia ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor

Oxidative stress is an important part of host innate immune response to foreign pathogens. However, the impact of vitamin C on oxidative stress and inflammation remains unclear in community-acquired pneumonia (CAP). We aimed to determine the effect of vitamin C on oxidative stress and inflammation. CAP patients were enrolled. Reactive oxygen species (ROS), DNA damage, superoxide dismutases (SOD) activity, tumor necrosis factor-alpha (TNF-α), and IL-6 were analyzed in CAP patients and LPS-stimulated macrophages cells. MH-S cells were transfected with RFP-LC3 plasmids. Autophagy was measured in LPS-stimulated macrophages cells. Severe CAP patients showed significantly increased ROS, DNA damage, TNF-α, and IL-6. SOD was significantly decreased in severe CAP. Vitamin C significantly decreased ROS, DNA damage, TNF-α, and IL-6. Vitamin C inhibited LPS-induced ROS, DNA damage, TNF-α, IL-6, and p38 in macrophages cells. Vitamin C inhibited autophagy in LPS-induced macrophages cells. These findings indicated that severe CAP exhibited significantly increased oxidative stress, DNA damage, and proinflammatory mediator. Vitamin C mitigated oxidative stress and proinflammatory mediator suggesting a possible mechanism for vitamin C in severe CAP.

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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 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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Herpes Simplex Virus 1 E3 Ubiquitin Ligase ICP0 Protein Inhibits Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Interacting with p65/RelA and p50/NF-κB1

Journal of Virology ◽

10.1128/jvi.01952-13 ◽

2013 ◽

Vol 87 (23) ◽

pp. 12935-12948 ◽

Cited By ~ 56

Author(s):

Jie Zhang ◽

Kezhen Wang ◽

Shuai Wang ◽

Chunfu Zheng

Keyword(s):

Tumor Necrosis Factor ◽

Ubiquitin Ligase ◽

Tumor Necrosis ◽

Nuclear Translocation ◽

E3 Ubiquitin Ligase ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Factor Alpha ◽

Necrosis Factor ◽

Hsv 1

NF-κB plays central roles in regulation of diverse biological processes, including innate and adaptive immunity and inflammation. HSV-1 is the archetypal member of the alphaherpesviruses, with a large genome encoding over 80 viral proteins, many of which are involved in virus-host interactions and show immune modulatory capabilities. In this study, we demonstrated that the HSV-1 ICP0 protein, a viral E3 ubiquitin ligase, was shown to significantly suppress tumor necrosis factor alpha (TNF-α)-mediated NF-κB activation. ICP0 was demonstrated to bind to the NF-κB subunits p65 and p50 by coimmunoprecipitation analysis. ICP0 bound to the Rel homology domain (RHD) of p65. Fluorescence microscopy demonstrated that ICP0 abolished nuclear translocation of p65 upon TNF-α stimulation. Also, ICP0 degraded p50 via its E3 ubiquitin ligase activity. The RING finger (RF) domain mutant ICP0 (ICP0-RF) lost its ability to inhibit TNF-α-mediated NF-κB activation and p65 nuclear translocation and degrade p50. Notably, the RF domain of ICP0 was sufficient to interact with p50 and abolish NF-κB reporter gene activity. Here, it is for the first time shown that HSV-1 ICP0 interacts with p65 and p50, degrades p50 through the ubiquitin-proteasome pathway, and prevents NF-κB-dependent gene expression, which may contribute to immune evasion and pathogenesis of HSV-1.

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Analysis of Subcellular RNA Fractions Revealed a Transcription-Independent Effect of Tumor Necrosis Factor Alpha on Splicing, Mediated by Spt5

Molecular and Cellular Biology ◽

10.1128/mcb.01117-15 ◽

2016 ◽

Vol 36 (9) ◽

pp. 1342-1353 ◽

Cited By ~ 10

Author(s):

Gil Diamant ◽

Tal Eisenbaum ◽

Dena Leshkowitz ◽

Rivka Dikstein

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Independent Effect ◽

Necrosis Factor Alpha ◽

Pol Ii ◽

Tnf Α ◽

Factor Alpha ◽

Induced Genes ◽

Necrosis Factor

The proinflammatory cytokine tumor necrosis factor alpha (TNF-α) modulates the expression of many genes, primarily through activation of NF-κB. Here, we examined the global effects of the elongation factor Spt5 on nascent and mature mRNAs of TNF-α-induced cells using chromatin and cytosolic subcellular fractions. We identified several classes of TNF-α-induced genes controlled at the level of transcription, splicing, and chromatin retention. Spt5 was found to facilitate splicing and chromatin release in genes displaying high induction rates. Further analysis revealed striking effects of TNF-α on the splicing of 25% of expressed genes; the vast majority were not transcriptionally induced. Splicing enhancement of noninduced genes by TNF-α was transient and independent of NF-κB. Investigating the underlying basis, we found that Spt5 is required for the splicing facilitation of the noninduced genes. In line with this, Spt5 interacts with Sm core protein splicing factors. Furthermore, following TNF-α treatment, levels of RNA polymerase II (Pol II) but not Spt5 are reduced from the splicing-induced genes, suggesting that these genes become enriched with a Pol II-Spt5 form. Our findings revealed the Pol II-Spt5 complex as a highly competent coordinator of cotranscriptional splicing.

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