Role of A20 in cIAP-2 Protection against Tumor Necrosis Factor α (TNF-α)-Mediated Apoptosis in Endothelial Cells

During the last decade, a growing corpus of evidence has indicated an important role of cytokines in the development of brain damage following cerebral ischemia. Tumor necrosis factor-α (TNF-α), a potent immunomodulator and pro-inflammatory cytokine, has been implicated in many pathological processes. In this study, we examined whether promoter region polymorphism in the TNF-α gene at position –308 affects the odds of cerebral infarction (CI) and whether genetic risk is enhanced by Sasang constitutional classification. Two hundred and twelve CI patients and 610 healthy controls were genotyped and determined according to Sasang constitutional classification. A significant decrease was found for the TNF-α A allele in CI patients compared with controls ( p = 0.033, odds ratio, OR: 0.622). However, there was no significant association between TNF-α polymorphism and Sasang constitution in CI patients. Our finding suggests that TNF-α promoter region polymorphism is responsible for susceptibility to CI in Koreans.

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Inhibition of Inflammation Mediated Through the Tumor Necrosis Factor α Biochemical Pathway Can Lead to Favorable Outcomes in Alzheimer Disease

Journal of Central Nervous System Disease ◽

10.1177/1179573517722512 ◽

2017 ◽

Vol 9 ◽

pp. 117957351772251 ◽

Cited By ~ 21

Author(s):

Daniah Shamim ◽

Michael Laskowski

Keyword(s):

Tumor Necrosis Factor ◽

Alzheimer Disease ◽

Immune Modulation ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Sodium Hydrosulfide ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Tumor necrosis factor α (TNF-α) inhibitors have long been used as disease-modifying agents in immune disorders. Recently, research has shown a role of chronic neuroinflammation in the pathophysiology of neurodegenerative diseases such as Alzheimer disease, and interest has been generated in the use of anti-TNF agents and TNF-modulating agents for prevention and treatment. This article extensively reviewed literature on animal studies testing these agents. The results showed a role for direct and indirect TNF-α inhibition through agents such as thalidomide, 3,6-dithiothalidomide, etanercept, infliximab, exendin-4, sodium hydrosulfide, minocycline, imipramine, and atorvastatin. Studies were performed on mice, rats, and monkeys, with induction of neurodegenerative physiology either through the use of chemical agents or through the use of transgenic animals. Most of these agents showed an improvement in cognitive function as tested with the Morris water maze, and immunohistochemical and histopathological staining studies consistently showed better outcomes with these agents. Brains of treated animals showed significant reduction in pro-inflammatory TNF-α and reduced the burden of neurofibrillary tangles, amyloid precursor protein, and β-amyloid plaques. Also, recruitment of microglial cells in the central nervous system was significantly reduced through these drugs. These studies provide a clearer mechanistic understanding of the role of TNF-α modulation in Alzheimer disease. All studies in this review explored the use of these drugs as prophylactic agents to prevent Alzheimer disease through immune modulation of the TNF inflammatory pathway, and their success highlights the need for further research of these drugs as therapeutic agents.

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In VitroProtective Effects of Two Extracts from Bergamot Peels on Human Endothelial Cells Exposed to Tumor Necrosis Factor-α (TNF-α)

Journal of Agricultural and Food Chemistry ◽

10.1021/jf1008605 ◽

2010 ◽

Vol 58 (14) ◽

pp. 8430-8436 ◽

Cited By ~ 32

Author(s):

Domenico Trombetta ◽

Francesco Cimino ◽

Mariateresa Cristani ◽

Giuseppina Mandalari ◽

Antonella Saija ◽

...

Keyword(s):

Endothelial Cells ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Human Endothelial Cells ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

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Baboon fetal arterial endothelial cells are more responsive to challenge by tumor necrosis factor α (TNF-α) than baboon fetal umbilical vein endothelial cells

Atherosclerosis ◽

10.1016/j.atherosclerosis.2010.06.030 ◽

2010 ◽

Vol 212 (2) ◽

pp. 701-703 ◽

Cited By ~ 1

Author(s):

A. Cerbulo-Vazquez ◽

M. Zavala ◽

G.A. Perez-Palacios ◽

S.L. Jenkins ◽

Luis D. Giavedoni ◽

...

Keyword(s):

Endothelial Cells ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Umbilical Vein ◽

Tnf Α ◽

Umbilical Vein Endothelial Cells ◽

Factor Α ◽

Arterial Endothelial Cells ◽

Necrosis Factor

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Interleukin-6 and tumor necrosis factor-α type 1 receptor deficient mice reveal a role of IL-6 and TNF-α on brain metallothionein-I and -III regulation

Molecular Brain Research ◽

10.1016/s0169-328x(98)00087-4 ◽

1998 ◽

Vol 57 (2) ◽

pp. 221-234 ◽

Cited By ~ 29

Author(s):

Javier Carrasco ◽

Joaquin Hernandez ◽

Horst Bluethmann ◽

Juan Hidalgo

Keyword(s):

Tumor Necrosis Factor ◽

Interleukin 6 ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Tnf Α ◽

Factor Α ◽

Deficient Mice ◽

Necrosis Factor

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Role of proteasome in regulation of tumor necrosis factor-α-induced endothelin-1 production in cultured vascular endothelial cells.

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)34478-6 ◽

1999 ◽

Vol 79 ◽

pp. 114

Author(s):

Mamoru Ohkita ◽

Masanori Takaoka ◽

Yutaka Kobayashi ◽

Eriko Itoh ◽

Hiroko Uemachi ◽

...

Keyword(s):

Endothelial Cells ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Endothelin 1 ◽

Factor Α ◽

Necrosis Factor

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Shiga Toxin Type 1 Activates Tumor Necrosis Factor-α Gene Transcription and Nuclear Translocation of the Transcriptional Activators Nuclear Factor-κB and Activator Protein-1

Blood ◽

10.1182/blood.v92.2.558.414k35_558_566 ◽

1998 ◽

Vol 92 (2) ◽

pp. 558-566 ◽

Cited By ~ 1

Author(s):

Ramesh Sakiri ◽

Belakere Ramegowda ◽

Vernon L. Tesh

Keyword(s):

Endothelial Cells ◽

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Nuclear Translocation ◽

Vascular Lesions ◽

Transcriptional Activators ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Shiga toxins (Stxs) produced by Shigella dysenteriae 1 andEscherichia coli have been implicated in the pathogenesis of bloody diarrhea, acute renal failure, and neurologic abnormalities. The pathologic hallmark of Stx-mediated tissue damage is the development of vascular lesions in which endothelial cells are swollen and detached from underlying basement membranes. However, in vitro studies using human vascular endothelial cells demonstrated minimal Stx-induced cytopathic effects, unless the target cells were also incubated with the proinflammatory cytokines tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β). These cytokines have been shown to upregulate the expression of the Stx-binding membrane glycolipid globotriaosylceramide (Gb3). We show here that purified Stx1 induces TNF secretion by a human monocytic cell line, THP-1, in a dose- and time-dependent manner. Treatment of cells with both lipopolysaccharides (LPS) and Stx1 results in augmented TNF production. Treatment with the nontoxic Gb3-binding subunit of Stx1 or with an anti-Gb3 monoclonal antibody did not trigger TNF production. Northern blot analyses show that Stx1 causes increased TNF-α production through transcriptional activation. Increased levels of TNF-α mRNA are preceded by the nuclear translocation of the transcriptional activators NF-κB and AP-1 and the loss of cytoplasmic IκB-α. These data are the first to show that, in addition to direct cytotoxicity, Stxs possess cellular signaling capabilities sufficient to induce the synthesis of cytokines that may be necessary for target cell sensitization and the development of vascular lesions.

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