Pro-inflammatory programmed cell death

Cookson, Brad T.; Brennan, Molly A.

doi:10.1016/s0966-842x(00)01936-3

Cited by 1,061 publications

(787 citation statements)

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“…FADD, FAS-associated death domain; TNFR1, TNF receptor 1; TRADD, TNF receptor-associated death domain; cIAP1, cellular inhibitor of apoptosis protein 1; RIP1, receptor-interacting protein 1; MLKL, mixed lineage kinase domain-like; cFLIP, cellular FLICE-like inhibitory proteins; MOMP, mitochondrial outer membrane permeabilization caspases, resulting in plasma membrane pore formation allowing water influx, cell swelling and osmotic lysis, followed by release of proinflammatory intracellular contents. 32,34 This demarcates it clearly from apoptosis where no loss of membrane integrity is observed. At the same time cytokines are secreted either through the newly formed plasma membrane pores or through microvesicles-or lysosomemediated exocytosis.…”

Section: Caspases In Non-apoptotic Cell Deathmentioning

confidence: 86%

“…30,31 This cell death was later characterized as a novel programmed cell death process, distinct from apoptosis. 32,33 Pyroptosis is a caspase-1-and -11-dependent cell death process and is considered an immune response to dispose of microbe-laden macrophages and clear intracellular pathogens in response to acute bacterial or viral infection or exposure to bacterial toxins. The process involves activation of these inflammatory Figure 2 Caspases in cell death pathways.…”

Section: Caspases In Non-apoptotic Cell Deathmentioning

confidence: 99%

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Old, new and emerging functions of caspases

et al. 2014

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Caspases are proteases with a well-defined role in apoptosis. However, increasing evidence indicates multiple functions of caspases outside apoptosis. Caspase-1 and caspase-11 have roles in inflammation and mediating inflammatory cell death by pyroptosis. Similarly, caspase-8 has dual role in cell death, mediating both receptor-mediated apoptosis and in its absence, necroptosis. Caspase-8 also functions in maintenance and homeostasis of the adult T-cell population. Caspase-3 has important roles in tissue differentiation, regeneration and neural development in ways that are distinct and do not involve any apoptotic activity. Several other caspases have demonstrated anti-tumor roles. Notable among them are caspase-2, -8 and -14. However, increased caspase-2 and -8 expression in certain types of tumor has also been linked to promoting tumorigenesis. Increased levels of caspase-3 in tumor cells causes apoptosis and secretion of paracrine factors that promotes compensatory proliferation in surrounding normal tissues, tumor cell repopulation and presents a barrier for effective therapeutic strategies. Besides this caspase-2 has emerged as a unique caspase with potential roles in maintaining genomic stability, metabolism, autophagy and aging. The present review focuses on some of these less studied and emerging functions of mammalian caspases.

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Section: Caspases In Non-apoptotic Cell Deathmentioning

confidence: 86%

Section: Caspases In Non-apoptotic Cell Deathmentioning

confidence: 99%

Old, new and emerging functions of caspases

et al. 2014

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“…[14][15][16]NF-kB-induced transcriptional priming of inflammasome proteins, followed by cation channel activation, cell volume expansion, and inflammasome component assembly. 17,18,20,21 NLRP3 is activated by diverse DAMP signals, including S100A9 homodimers and S100A8/9 heterodimers that function as alarmins that converge upon NADPH oxidase to generate reactive oxygen species (ROS). [21][22][23] Here, we show that S100A9 and ROS, generated in response to NLRP3 inflammasome activation or somatic gene mutations, serve as DAMP signaling intermediates responsible for inflammasomemediated pyroptosis and b-catenin activation in MDSs.…”

Section: Introductionmentioning

confidence: 99%

The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype

Basiorka¹,

McGraw²,

Eksioglu³

et al. 2016

Blood

284

350

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Key Points• Key biological features of MDSs are explained by NLRP3 inflammasome activation, which drives pyroptotic cell death and b-catenin activation.• Alarmin signals and founder gene mutations license this redox-sensitive inflammasome platform.Despite genetic heterogeneity, myelodysplastic syndromes (MDSs) share features of cytological dysplasia and ineffective hematopoiesis. We report that a hallmark of MDSs is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death. Independent of genotype, MDS hematopoietic stem and progenitor cells (HSPCs) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of interleukin-1b (IL-1b) and IL-18, and pyroptotic cell death. Mechanistically, pyroptosis is triggered by the alarmin S100A9 that is found in excess in MDS HSPCs and bone marrow plasma. Further, like somatic gene mutations, S100A9-induced signaling activates NADPH oxidase (NOX), increasing levels of reactive oxygen species (ROS) that initiate cation influx, cell swelling, and b-catenin activation. Notably, knockdown of NLRP3 or caspase-1, neutralization of S100A9, and pharmacologic inhibition of NLRP3 or NOX suppress pyroptosis, ROS generation, and nuclear b-catenin in MDSs and are sufficient to restore effective hematopoiesis. Thus, alarmins and founder gene mutations in MDSs license a common redox-sensitive inflammasome circuit, which suggests new avenues for therapeutic intervention. (Blood. 2016;128(25):2960-2975

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“…Together with necroptosis it has been recently classified as a form of programmed necrosis, where a major role is played by the proinflammatory caspases 1 and 11 in mouse, while in humans the latter is replaced by caspases 4 and 5 (Cookson and Brennan, 2001;Averette et al, 2009;Lamkanfi and Dixit, 2014;Wallach et al, 2016). The process is started by the activation of intracellular nucleotide oligomerisation domain-like recognition receptors (NLRs) that form the inflammasome together with the apoptosisassociated speck-like protein containing a CARD (ASC), which enable pro-caspase 1 activation.…”

Section: Pyroptosismentioning

confidence: 99%

Lysosomes in programmed cell death pathways: from initiators to amplifiers

Kavčič

Pegan

Turk

2016

Biological Chemistry

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Lysosome is the central organelle for intracellular degradation of biological macromolecules and organelles. The material destined for degradation enters the lysosomes primarily via endocytosis, autophagy and phagocytosis, and is degraded through the concerted action of more than 50 lysosomal hydrolases. However, lysosomes are also linked with numerous other processes, including cell death, inflammasome activation and immune response, as well as with lysosomal secretion and cholesterol recycling. Among them programmed cell death pathways including apoptosis have received major attention. In most of these pathways, cell death was accompanied by lysosomal membrane permeabilization and release of lysosomal constituents with an involvement of lysosomal hydrolases, including the cathepsins. However, it is less clear, whether lysosomal membrane permeabilization is really critical for the initiation of cell death programme(s). Therefore, the role of lysosomal membrane permeabilization in various programmed cell death pathways is reviewed, as well as the mechanisms leading to it.

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Pro-inflammatory programmed cell death

Cited by 1,061 publications

References 10 publications

Old, new and emerging functions of caspases

Old, new and emerging functions of caspases

The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype

Lysosomes in programmed cell death pathways: from initiators to amplifiers

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