MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members

Despite overwhelming evidence that enhanced production of the p75 tumor necrosis factor receptor (p75TNF-R) accompanies development of specific human inflammatory pathologies such as multi-organ failure during sepsis, inflammatory liver disease, pancreatitis, respiratory distress syndrome, or AIDS, the function of this receptor remains poorly defined in vivo. We show here that at levels relevant to human disease, production of the human p75TNF-R in transgenic mice results in a severe inflammatory syndrome involving mainly the pancreas, liver, kidney, and lung, and characterized by constitutively increased NF-κB activity in the peripheral blood mononuclear cell compartment. This process is shown to evolve independently of the presence of TNF, lymphotoxin α, or the p55TNF-R, although coexpression of a human TNF transgene accelerated pathology. These results establish an independent role for enhanced p75TNF-R production in the pathogenesis of inflammatory disease and implicate the direct involvement of this receptor in a wide range of human inflammatory pathologies.

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Phytochemicals against TNFα-Mediated Neuroinflammatory Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21030764 ◽

2020 ◽

Vol 21 (3) ◽

pp. 764 ◽

Cited By ~ 3

Author(s):

Lalita Subedi ◽

Si Eun Lee ◽

Syeda Madiha ◽

Bhakta Prasad Gaire ◽

Mirim Jin ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Critical Role ◽

Tumor Necrosis Factor Receptor ◽

Inflammatory Disorder ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Necrosis Factor

Tumor necrosis factor-alpha (TNF-α) is a well-known pro-inflammatory cytokine responsible for the modulation of the immune system. TNF-α plays a critical role in almost every type of inflammatory disorder, including central nervous system (CNS) diseases. Although TNF-α is a well-studied component of inflammatory responses, its functioning in diverse cell types is still unclear. TNF-α functions through its two main receptors: tumor necrosis factor receptor 1 and 2 (TNFR1, TNFR2), also known as p55 and p75, respectively. Normally, the functions of soluble TNF-α-induced TNFR1 activation are reported to be pro-inflammatory and apoptotic. While TNF-α mediated TNFR2 activation has a dual role. Several synthetic drugs used as inhibitors of TNF-α for diverse inflammatory diseases possess serious adverse effects, which make patients and researchers turn their focus toward natural medicines, phytochemicals in particular. Phytochemicals targeting TNF-α can significantly improve disease conditions involving TNF-α with fewer side effects. Here, we reviewed known TNF-α inhibitors, as well as lately studied phytochemicals, with a role in inhibiting TNF-α itself, and TNF-α-mediated signaling in inflammatory diseases focusing mainly on CNS disorders.

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CrmE, a Novel Soluble Tumor Necrosis Factor Receptor Encoded by Poxviruses

Journal of Virology ◽

10.1128/jvi.75.1.226-233.2001 ◽

2001 ◽

Vol 75 (1) ◽

pp. 226-233 ◽

Cited By ~ 88

Author(s):

Margarida Saraiva ◽

Antonio Alcami

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis ◽

Molecular Mimicry ◽

Critical Role ◽

Tumor Necrosis Factor Receptor ◽

Binding Activity ◽

Cytolytic Activity ◽

Cowpox Virus ◽

Cytokines And Chemokines ◽

Necrosis Factor

ABSTRACT Cytokines and chemokines play a critical role in both the innate and acquired immune responses and constitute prime targets for pathogen sabotage. Molecular mimicry of cytokines and cytokine receptors is a mechanism encoded by large DNA viruses to modulate the host immune response. Three tumor necrosis factor receptors (TNFRs) have been identified in the poxvirus cowpox virus. Here we report the identification and characterization of a fourth distinct soluble TNFR, named cytokine response modifier E (CrmE), encoded by cowpox virus. ThecrmE gene has been sequenced in strains of the orthopoxviruses cowpox virus, ectromelia virus, and camelpox virus, and was found to be active in cowpox virus. crmE is expressed as a secreted 18-kDa protein with TNF binding activity. CrmE was produced in the baculovirus and vaccinia virus expression systems and was shown to bind human, mouse, and rat TNF, but not human lymphotoxin α, conjugates of lymphotoxins α and β, or seven other ligands of the TNF superfamily. However, CrmE protects cells only from the cytolytic activity of human TNF. CrmE is a new member of the TNFR superfamily which is expressed as a soluble molecule that blocks the binding of TNF to high-affinity TNFRs on the cell surface. The remarkable finding of a fourth poxvirus-encoded TNFR suggests that modulation of TNF activity is complex and represents a novel viral immune evasion mechanism.

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