INHIBITED NEUTROPHIL APOPTOSIS: PROTEASOME DEPENDENT NF-κB TRANSLOCATION IS REQUIRED FOR TRAF-1 SYNTHESIS

Nolan, Brian; Kim, Robin; Duffy, Andrew; Sheth, Ketan; De, Mita; Miller, Carol; Chari, Ravi; Bankey, Paul E.

doi:10.1097/00024382-200014030-00008

Cited by 33 publications

(27 citation statements)

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“…It has also been reported that incubation with some of these agents leads to the activation of NF-κB [23]. Furthermore, a major induction of human neutrophil apoptosis was seen after inhibiting NF-κB [21,29,30,43]. These data strongly suggest that NF-κB is a major regulator of the human neutrophil life span.…”

Section: S Notebaert Et Almentioning

confidence: 72%

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NF-?B inhibition accelerates apoptosis of bovine neutrophils

2005

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-Apoptosis is one of the major events that contribute to the regulation of the immune system. For human neutrophils, evidence has been produced that the transcription factor NF-κB is critical in influencing the ultimate outcome of a cell's fate. However, such research has not yet been performed on bovine neutrophils. This urged us to examine the possible involvement of NF-κB in apoptosis of these cells. At first, we investigated whether p65 and p50, the most important members of the NF-κB family, are expressed in isolated blood neutrophils. The presence of both members was demonstrated on the RNA and protein level. Then the effect on bovine neutrophil apoptosis of gliotoxin, a potent and specific inhibitor of NF-κB, was examined. The rate of constitutive apoptosis was found to be greatly accelerated by inhibition of NF-κB. Furthermore, gliotoxin dramatically augmented the limited pro-apoptotic effect of TNF-α, an important inflammatory mediator. The results were obtained in six cows by annexin-V-FITC staining of externalized phosphatidylserine and subsequent flow cytometric analysis. Additional measurement of caspase-3/7 activity and evaluation of morphological criteria confirmed the outcome of this experiment. Finally, NF-κB activity was assessed under these conditions. The activity of p50 was found to be minimally affected by gliotoxin, while significantly lower active p65 values were observed. Still, the highest percentage of apoptosis, which was caused by incubation with both gliotoxin and TNF-α, did not correspond to the lowest activity of p65. We conclude that NF-κB p65 promotes the survival of bovine neutrophils by delaying the initiation of apoptosis.bovine neutrophil / NF-κB / apoptosis

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Section: S Notebaert Et Almentioning

confidence: 72%

“…Various studies with human neutrophils have shown that NF-κB plays a crucial protective role against apoptosis [21,29,30,43]. In the next part of the current study, p65 and p50 activities were therefore examined to evaluate whether this also applies to bovine neutrophils.…”

Section: Discussionmentioning

confidence: 96%

NF-?B inhibition accelerates apoptosis of bovine neutrophils

2005

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“…TNF-␣ is a unique proinflammatory cytokine whose signaling is linked to both antiapoptotic and proapoptotic pathways (3,10,12,23,39,42,54). The cellular response to TNF-␣ is dependent on cytokine levels, length of exposure, and input from other signaling pathways (i.e., engagement of integrins).…”

Section: Discussionmentioning

confidence: 99%

“…The increased survival of neutrophils may contribute to the pathophysiology of these inflammatory diseases through excessive release of toxic mediators, resulting in host tissue damage and organ dysfunction. Tumor necrosis factor (TNF)-␣ and other proinflammatory cytokines have been implicated as endogenous mediators responsible for the modulation of neutrophil apoptosis during inflammation (10,12,14,18,22,23,27,31,34,37,39,42,54).…”

mentioning

confidence: 99%

“…TNF-␣ is a unique proinflammatory cytokine whose signaling pathways are linked to both antiapoptotic and proapoptotic responses in neutrophils (3,10,12,23,39,42,54). Neutrophils possess two TNF-␣ receptors, a 55-60 kDa (p60TNFR) and a 75-80 kDa (p80TNFR), and both antiapoptotic and proapoptotic signaling pathways are regulated principally by the p60TNFR (4,33,49).…”

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confidence: 99%

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A role for PKC-δ and PI 3-kinase in TNF-α-mediated antiapoptotic signaling in the human neutrophil

Kilpatrick

Lee

Haines

et al. 2002

American Journal of Physiology-Cell Physiology

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The proinflammatory cytokine tumor necrosis factor (TNF)-α has been implicated in the attenuation of neutrophil spontaneous apoptosis during sepsis. Antiapoptotic signaling is principally mediated through the p60TNF receptor (p60TNFR). In neutrophils, TNF-α is an incomplete secretagogue and requires input from a ligated integrin(s) for neutrophil activation. In adherent neutrophils, TNF-α triggers association of both protein kinase C (PKC)-δ and phosphatidylinositol (PI) 3-kinase with the p60TNFR. In this study, a role for PKC-δ and PI 3-kinase in TNF-α-mediated antiapoptotic signaling was examined. TNF-α inhibited spontaneous apoptosis in fibronectin-adherent neutrophils, and this antiapoptotic signaling was blocked by the PKC-δ inhibitor rottlerin, but not by an inhibitor of Ca2+-dependent PKC isotypes, Go-6976. Inhibition of PI 3-kinase by LY-294002 also inhibited TNF-α-mediated antiapoptotic signaling. Cycloheximide blocked TNF-α-mediated antiapoptotic signaling, suggesting protein synthesis is required. Inhibition of either PKC-δ or PI 3-kinase attenuated TNF-α-mediated activation of the antiapoptotic transcription factor NFκB. Thus both PKC-δ and PI 3-kinase have essential roles in TNF-α-mediated antiapoptotic signaling in adherent neutrophils.

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Trauma‐associated human neutrophil alterations revealed by comparative proteomics profiling

Zhang

Krovvidi

Gao

et al. 2013

Proteomics Clinical Apps

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PURPOSE Polymorphonuclear neutrophils (PMNs) play an important role in mediating the innate immune response after severe traumatic injury; however, the cellular proteome response to traumatic condition is still largely unknown. EXPERIMENTAL DESIGN We applied 2D-LC-MS/MS based shotgun proteomics to perform comparative proteome profiling of human PMNs from severe trauma patients and healthy controls. RESULTS A total of 197 out of ~2500 proteins (being identified with at least two peptides) were observed with significant abundance changes following the injury. The proteomics data were further compared with transcriptomics data for the same genes obtained from an independent patient cohort. The comparison showed that the protein abundance changes for the majority of proteins were consistent with the mRNA abundance changes in terms of directions of changes. Moreover, increased protein secretion was suggested as one of the mechanisms contributing to the observed discrepancy between protein and mRNA abundance changes. Functional analyses of the altered proteins showed that many of these proteins were involved in immune response, protein biosynthesis, protein transport, NRF2-mediated oxidative stress response, the ubiquitin-proteasome system, and apoptosis pathways. CONCLUSIONS AND CLINICAL RELEVANCE Our data suggest increased neutrophil activation and inhibited neutrophil apoptosis in response to trauma. The study not only reveals an overall picture of functional neutrophil response to trauma at the proteome level, but also provides a rich proteomics data resource of trauma-associated changes in the neutrophil that will be valuable for further studies of the functions of individual proteins in PMNs.

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INHIBITED NEUTROPHIL APOPTOSIS: PROTEASOME DEPENDENT NF-κB TRANSLOCATION IS REQUIRED FOR TRAF-1 SYNTHESIS

Cited by 33 publications

References 0 publications

NF-?B inhibition accelerates apoptosis of bovine neutrophils

NF-?B inhibition accelerates apoptosis of bovine neutrophils

A role for PKC-δ and PI 3-kinase in TNF-α-mediated antiapoptotic signaling in the human neutrophil

Trauma‐associated human neutrophil alterations revealed by comparative proteomics profiling

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