Surviving apoptosis: life–death signaling in single cells

Flusberg, Deborah; Sorger, Peter K.

doi:10.1016/j.tcb.2015.03.003

Cited by 127 publications

(87 citation statements)

References 184 publications

(209 reference statements)

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“…31 TNF receptors, present in several cell types, recognize this cytokine and promote different effects such as cell death/survival, cell differentiation, proliferation/migration, increased tissue permeability and leucocyte adhesion. 31 An important feature of TNF-a is the capacity to induce apoptosis under certain conditions, 32 as for example when the nuclear factor-jB pathway is blocked. 33 IL-10 can inhibit nuclear factor-jB (NF-kB) by the induction of p50/p50 homodimerization and its nuclear translocation; 34 therefore in the presence of IL-10, TNF-a will induce cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae

et al. 2015

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Summary Streptococcus pneumoniae is a major aetiological agent of pneumonia worldwide, as well as otitis media, sinusitis, meningitis and sepsis. Recent reports have suggested that inflammation of lungs due to S. pneumoniae infection promotes bacterial dissemination and severe disease. However, the contribution of anti‐inflammatory molecules to the pathogenesis of S. pneumoniae remains unknown. To elucidate whether the production of the anti‐inflammatory cytokine interleukin‐10 (IL‐10) is beneficial or detrimental for the host during pneumococcal pneumonia, we performed S. pneumoniae infections in mice lacking IL‐10 (IL‐10−/− mice). The IL‐10−/− mice showed increased mortality, higher expression of pro‐inflammatory cytokines, and an exacerbated recruitment of neutrophils into the lungs after S. pneumoniae infection. However, IL‐10−/− mice showed significantly lower bacterial loads in lungs, spleen, brain and blood, when compared with mice that produced this cytokine. Our results support the notion that production of IL‐10 during S. pneumoniae infection modulates the expression of pro‐inflammatory cytokines and the infiltration of neutrophils into the lungs. This feature of IL‐10 is important to avoid excessive inflammation of tissues and to improve host survival, even though bacterial dissemination is less efficient in the absence of this cytokine.

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Section: Discussionmentioning

confidence: 99%

Interleukin‐10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae

et al. 2015

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“…The correct regulation of programmed cell death is critical for developmental homeostasis and normal morphogenesis of embryonic tissues (Flusberg & Sorger, 2015). Apoptosis can be triggered by intrinsic and extrinsic factors, the intrinsic pathway involving mitochondrial events driven by Bcl-2 family proteins (Ulukaya, Acilan, & Yilmaz, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…Bcl-2 family proteins are well known as key initiators of the apoptotic cascade (Moldoveanu, Follis, Kriwacki, & Green, 2014), and a balance between anti-and proapoptotic members determines cell fate (Flusberg & Sorger, 2015), contributing to normal development and organ shape as shown in several in vivo models. Complete absence of both pro-apoptotic proteins Bax and Bak results in either prenatal lethality or severe defects in several tissues after birth (Lindsten et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Apoptosis-associated protein expression in human salivary gland morphogenesis

Teshima

Ianez

Coutinho‐Camillo

et al. 2016

Archives of Oral Biology

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Objective: Salivary gland (SG) development is based on branching morphogenesis, in which programmed cell death has been proposed to play a role in cell signalling and organ shaping.In the mouse salivary gland apoptosis has been suggested to play a key role in lumen formation, removing the central cells of the epithelial stalks. Here we analyse the expression of several anti-and pro-regulators of apoptosis during human SG development in a range of developmental stages.Design: Foetal SGs obtained from the University of São Paulo were analysed by immunohistochemistry to assess the expression of apoptosis-associated proteins: caspases (caspase-6, -7, -9 and cleaved caspase-3), Bcl-2 family members (Bax, Bak, Bad, Bid, Bcl-2, Bcl-x and Bcl-xL), Survivin (BIRC5), Cytochrome C and Apaf-1.Results: Nuclear expression of Bax and Bak was identified in presumptive luminal areas at initial stages, while Bcl-xL showed the most relevant anti-apoptotic activity. Caspase-6, -7 and -9 were expressed during all stages, while interestingly cleaved caspase-3 showed no prominent expression, indicating that caspase-7 is the main effector. Apoptosome complex components Apaf-1 and Cytochrome C, as well as survivin were all positive in developing glands. Conclusions:The particular expression pattern of several apoptotic regulators in human SG development suggests the existence of a fundamental role for apoptosis during duct formation. The absence of Bad and Bid expressions indicates that the instrinsic pathway is more active then the extrinsic during human gland formation. The subcellular localisation of intrinsic-apoptosis proteins correlated with apoptotic activity, but also suggested additional non-apoptotic functions. Highlights: Caspase-7 is the main executioner caspase involved in human SG duct development  Consistent cytoplasmic expression suggest additional non-apoptotic functions  Intrinsic-type apoptotic pathway drives human SG development

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“…Additionally, NF-κB pathway featured protein p-NF-κB and p-IκB was activated after either TRAIL or irradiation treatment. Activation of NF-κB pathway could inhibit apoptosis via expression of anti-apoptotic protein [38,39], which could explain NF-κB pathway involved in the TRAIL resistance and irradiation resistance in GSLCs. However, when combined treatment with TRAIL and IR, the expression of p-NF-κB and p-IκB was neither decreased nor increased.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effect of TRAIL and irradiation in elimination of glioblastoma stem-like cells

et al. 2018

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Glioblastoma multiforme (GBM) is the most common malignancy in central nervous system. A small subpopulation of GBM cells known as GBM stem-like cells (GSLCs) were supposed to be the most malignant cells among GBM cells as they are resistant to multiple therapies including radiotherapy. In this study, we set up two GSLCs cell lines from the two parental U87 and U251 glioma cell lines, and studied the expression of apoptosis-related genes alteration in GSLCs before and after irradiation. We found that one of the receptors of TNF-related apoptosis-inducing ligand (TRAIL), DR5, was dramatically up-regulated in GSLCs after irradiation (IR). Although GSLCs are resistant to both TRAIL and radiation treatment alone, the combined treatment with TRAIL and irradiation achieved maximum killing effect of GSLCs due to inducing the expression of DR5 and inhibiting the expression of cFLIP. Therefore, TRAIL and IR combined treatment would be a simple but practical therapeutic strategy for clinical application.

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Surviving apoptosis: life–death signaling in single cells

Cited by 127 publications

References 184 publications

Interleukin‐10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae

Interleukin‐10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae

Apoptosis-associated protein expression in human salivary gland morphogenesis

Synergistic effect of TRAIL and irradiation in elimination of glioblastoma stem-like cells

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