Tumor necrosis factor alpha (TNFα) plays a critical role in the pathogenesis of ischemia-reperfusion-induced gastric injury

The transcription factor NF-κB plays a critical role in diverse biological processes. The NF-κB pathway can be activated by incoming pathogens and then stimulates both innate and adaptive immunity. However, many viruses have evolved corresponding strategies to balance NF-κB activation to benefit their replication. Pseudorabies virus (PRV) is an economically important pathogen that belongs to the alphaherpesvirus group. There is little information about PRV infection and NF-κB regulation. This study demonstrates for the first time that the UL24 protein could abrogate tumor necrosis factor alpha (TNF-α)-mediated NF-κB activation. An overexpression assay indicated that UL24 inhibits this pathway at or downstream of P65. Furthermore, co-immunoprecipitation analysis demonstrated that UL24 selectively interacts with P65. We demonstrated that UL24 could significantly degrade P65 by the proteasome pathway. For the first time, PRV UL24 was shown to play an important role in NF-κB evasion during PRV infection. This study expands our understanding that PRV can utilize its encoded protein UL24 to evade NF-κB signaling.

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Pentoxifylline inhibits liver expression of tumor necrosis factor alpha mRNA following normothermic ischemia-reperfusion

HPB ◽

10.1080/13651820701272292 ◽

2007 ◽

Vol 9 (2) ◽

pp. 112-119 ◽

Cited By ~ 21

Author(s):

Alaa El-Ghoneimi ◽

Raffaele Cursio ◽

Annie Schmid-Alliana ◽

Michel Tovey ◽

Ahmed Lasfar ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Ischemia Reperfusion ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

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Tumor necrosis factor-$alpha; does not modulate ischemia/reperfusion injury in na�ve myocardium but is essential for the development of late preconditioning*1

Journal of Molecular and Cellular Cardiology ◽

10.1016/s0022-2828(04)00082-3 ◽

2004 ◽

Author(s):

B DAWN

Keyword(s):

Tumor Necrosis Factor ◽

Reperfusion Injury ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Necrosis Factor Alpha ◽

Late Preconditioning ◽

Factor Alpha ◽

Necrosis Factor

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Regulation of 92-kD gelatinase release in HL-60 leukemia cells: tumor necrosis factor-alpha as an autocrine stimulus for basal- and phorbol ester-induced secretion

Blood ◽

10.1182/blood.v83.12.3638.bloodjournal83123638 ◽

1994 ◽

Vol 83 (12) ◽

pp. 3638-3646 ◽

Cited By ~ 1

Author(s):

C Ries ◽

H Kolb ◽

PE Petrides

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Critical Role ◽

Leukemia Cells ◽

Tnf Alpha ◽

Enzyme Release ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

Matrix metalloproteinase 9 (MMP-9), also known as 92-kD type IV collagenase/gelatinase, is believed to play a critical role in tumor invasion and metastasis. Here, we report that MMP-9 was constitutively released from the human promyelocytic cell line HL-60 as determined by zymographic analysis. Tumor necrosis factor-alpha (TNF-alpha) enhanced the enzyme release threefold to fourfold and the protein kinase C (PKC) activator and differentiation inducer 12-O-tetradecanoylphorbol-13- acetate (TPA) eightfold to ninefold. Gelatinase induction by TNF-alpha and TPA was inhibited by actinomycin D or cycloheximide, indicating that de novo protein synthesis was required. Neutralizing monoclonal antibodies to TNF-alpha (anti-TNF-alpha) decreased the basal MMP-9 release of these cells. In addition, these antibodies also significantly interfered with the TPA-induced enzyme release. Agents that inhibit TNF-alpha expression in HL-60 cells, such as pentoxifylline and dexamethasone, completely abrogated both the constitutive and TPA-evoked MMP-9 release. Diethyldithiocarbamate, which is known to stimulate TNF-alpha production in HL-60 cells, exerted a positive effect on MMP-9 release in untreated cells but was inhibitory in TPA-treated HL-60 cells. The PKC inhibitor staurosporine at low concentrations (100 ng/mL) caused a significant augmentation of MMP-9 release in untreated cultures that was blocked by the addition of anti-TNF-alpha. High concentrations (2 mumol/L) of staurosporine completely abolished the extracellular enzyme activity both in untreated and TPA-stimulated cells. These results suggest, that TNF- alpha is required for basal and PKC-mediated MMP-9 release in HL-60 leukemia cells. Thus, MMP-9 secretion may be regulated by TNF-alpha not only in a paracrine but also in an autocrine fashion. This may potentiate the matrix degradative capacity of immature leukemic cells in the processes of bone marrow egress and the evasion of these cells into peripheral tissue.

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