Biological and biochemical inhibitors of the NF-κB/Rel proteins and cytokine synthesis

Beauparlant, Pierre; Hiscott, John

doi:10.1016/1359-6101(96)00020-2

Cited by 123 publications

(82 citation statements)

References 117 publications

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“…To confirm that the κB-site-binding activity induced by HSV-2 infection is essential for the synergistic effect of HSV-2 infection on IFN-γ-induced NO production, we examined NO production of IFN-γ-activated and virus-infected macrophages in the presence and absence of PDTC, an inhibitor of NF-κB activation (Beauparlant & Hiscott, 1996). As seen in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To address the first question, we used TPCK, which inhibits NF-κB activation through a different mechanism to PDTC. The antioxidant PDTC is thought to inhibit NF-κB activation by depleting the cells of oxygen radicals, believed to be involved in activation, whereas TPCK acts by inhibiting proteasome function and hence IκB degradation (Beauparlant & Hiscott, 1996). Inhibition of NF-κB activation with TPCK had the same effect as with PDTC (data not shown), thereby strongly indicating that the effect of HSV-2 infection and TNF-α treatment on IFN-γ-induced NO production is mediated by NF-κB.…”

Section: Discussionmentioning

confidence: 99%

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NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages.

Paludan

Ellermann-Eriksen²,

Mogensen³

1998

Journal of General Virology

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Nitric oxide (NO), produced in interferon (IFN)-γ-activated murine macrophages by the enzyme inducible nitric oxide synthase (iNOS), has been found to have antiviral properties. We have previously shown that herpes simplex virus type 2 (HSV-2) infection of macrophages synergistically enhances IFN-γ-induced NO production, and we now extend these findings by providing evidence that virusinduced tumour necrosis factor (TNF)-α mediates activation of the transcription factor nuclear factor (NF)-κB, which in turn is responsible for the synergistic effect. HSV-2 infection and IFN-γ stimulation of macrophages synergistically induced TNF-α secretion and nuclear translocation of NF-κB, which bound to a sequence corresponding to a κB site in the iNOS promoter. The effect of HSV-2 on NF-κB and NO production was eliminated when cells were

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages.

Paludan

Ellermann-Eriksen²,

Mogensen³

1998

Journal of General Virology

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“…In addition, since a decrease in NF-kB activation is controlled by the amount of IkB inhibitory proteins, we evaluated NA and NAM modulation of the protein levels of IkB-a, IkB-b and IkB-g, three major members of the IkB family of NF-kB inhibitors. 75,76 We found that the protein levels of IkB-g were increased over that of control cells after pretreatment with NA but not with NAM ( Figure 6). These findings indicate that one way in which both NA and NAM can decrease activated NF-kB is through a down regulation of NF-kB(p50) and NF-kB(p65) protein levels.…”

Section: Nicotinic Acid and Nicotinamide Do Not Affect Cellular Prolimentioning

confidence: 85%

The NAD+ precursors, nicotinic acid and nicotinamide protect cells against apoptosis induced by a multiple stress inducer, deoxycholate

et al. 2000

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The bile salt, sodium deoxycholate (NaDOC), is a natural detergent that promotes digestion of fats. At high physiologic levels, NaDOC activates many stress-response pathways and induces apoptosis in various cell types. NaDOC induces DNA damage and activates poly(ADP-ribose) polymerase (PARP), an enzyme that utilizes NAD + as a substrate to repair DNA. NaDOC also induces oxidative stress, endoplasmic reticulum (ER) stress and contributes to protein malfolding. The NAD + precursors, nicotinic acid (NA) and nicotinamide (NAM) were found to protect cells against NaDOC-induced apoptosis. NA and NAM also decreased constitutive levels of both activated NF-kB and GRP78, two proteins that respond to oxidative stress. However, the mechanism by which NA and NAM protects cells against apoptosis does not involve a reduction in constitutive levels of oxidative stress. NA or NAM treatment increased the protein levels of glyceraldehyde-3-phosphate dehydrogense (GAPDH), a multi-functional enzyme, in the nucleus and cytoplasm, respectively. NAM did not activate the promoter/response elements of 13 stress response genes nor reduce intracellular non-protein thiols, suggesting that it is non-toxic to cells. NAM thus has promise as a dietary supplement to help prevent disorders involving excessive apoptosis. Cell Death and Differentiation (2000) 7, 314 ± 326.

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“…The NF-kB pathway is well known for its role in the transcriptional activation of several cytokine related genes, such as TNFa, TNFb, IL-1, IL-2, IL-6, and IL-8 (Baeuerle and Baichwal, 1997;Beauparlant and Hiscott, 1996). Therefore, the NF-kB activating ability of ORF-K13 may have important implications for the natural history of Kaposi's Sarcoma (KS).…”

Section: Discussionmentioning

confidence: 99%

Modulation of the NF-κB pathway by virally encoded Death Effector Domains-containing proteins

et al. 1999

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Death E ector Domains (DEDs) have been known to mediate the recruitment of Caspase 8 and its homologs to the aggregated death-inducing signaling complex (DISC), consisting of the death domain (DD)-containing receptors and various signaling proteins. In addition, several viruses were recently shown to encode proteins with DEDs (also called FLICE inhibitory proteins or vFLIPs) which have the ability of blocking cell death induced by DD-containing receptors. We provide evidence that vFLIPs can also modulate the NF-kB pathway and physically interact with several signaling proteins, such as the TRAFs, RIP, NIK and the IKKs. Modulation of the NF-kB pathway may play a role in the natural history of infection by these viruses.

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Biological and biochemical inhibitors of the NF-κB/Rel proteins and cytokine synthesis

Cited by 123 publications

References 117 publications

NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages.

NF-kappaB activation is responsible for the synergistic effect of herpes simplex virus type 2 infection on interferon-gamma-induced nitric oxide production in macrophages.

The NAD+ precursors, nicotinic acid and nicotinamide protect cells against apoptosis induced by a multiple stress inducer, deoxycholate

Modulation of the NF-κB pathway by virally encoded Death Effector Domains-containing proteins

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