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https://www.readbyqxmd.com/read/28525771/return-of-the-ice-age-caspases-safeguard-against-inflammatory-cell-death
#1
Marcin Poreba, Guy Salvesen
In a recent issue of Cell Chemical Biology, Taabazuing et al. (2017) reveal a bidirectional interplay between pathways leading to apoptosis and pyroptosis, two forms of regulated cell death with opposing inflammatory outcomes. The outcome is sealed by differential cleavage of the key pyroptosis execution substrate gasdermin D such that inflammatory caspases activate it but apoptotic caspases prevent its activation.
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28516117/reconstruction-of-the-mouse-inflammasome-system-in-hek293t-cells
#2
Hexin Shi, Anne Murray, Bruce Beutler
The NLRP3 (NLR family, Pyrin domain containing 3) inflammasome is a multiprotein complex comprised of NLRP3, pro-caspase-1, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and the protein kinase NIMA related kinase 7 (NEK7) (Shi et al., 2016; He et al., 2016; Schmid-Burgk et al., 2016). When cells are exposed to microbes and/or danger signals, the inflammasome assembles and serves as a platform for the activation of caspase-1. Caspase-1 activation promotes the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-18, and IL-33 as well as pyroptosis induction (Gross et al...
November 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28516116/asc-particle-induced-peritonitis
#3
Lucia de Almeida, Andrea Dorfleutner, Christian Stehlik
In response to pathogen infection and tissue damage, inflammasome sensors such as NLRP3 and AIM2 are activated, which triggers PYRIN domain (PYD)-mediated ASC nucleation, followed by self-perpetuating ASC polymerization, which ultimately culminates in caspase-1 activation, interleukin (IL)-1β and IL-18 processing and release and pyroptosis (Ratsimandresy et al., 2013; Cai et al., 2014). Inflammasomes release not only cytokines, but also the polymeric ASC danger particles (pASC) by pyroptosis, which perpetuate and propagate inflammasome responses to bystander cells to engage cell intrinsic ASC and caspase-1 (Baroja-Mazo et al...
October 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28515339/chemotherapy-treated-cells-go-up-in-flames
#4
Kristopher Sarosiek
Apoptosis induced by chemotherapies can also trigger proinflammatory pyroptosis.
May 17, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28500028/chemotherapy-activated-caspase-3-cleaves-gsdme-to-drive-pyroptosis
#5
(no author information available yet)
GSMDE promotes a switch of chemotherapy-mediated cell death from apoptosis to pyroptosis.
May 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28498362/caspases-and-their-substrates
#6
REVIEW
Olivier Julien, James A Wells
Protease biology is intimately linked to the functional consequences of substrate cleavage events. Human caspases are a family of 12 fate-determining cysteine proteases that are best known for driving cell death, either apoptosis or pyroptosis. More recently, caspases have been shown to be involved in other cellular remodeling events as well including stem cell fate determination, spermatogenesis, and erythroid differentiation. Recent global proteomics methods enable characterization of the substrates that caspases cleave in live cells and cell extracts...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28477436/brain-inflammasomes-in-stroke-and-depressive-disorders-regulation-by-estrogen
#7
REVIEW
Alexander Slowik, Leoni Lammerding, Stefanie Hoffmann, Cordian Beyer
Neuroinflammation is a devastating pathophysiological process which ends up in brain damage and neuronal death. Pathogens, cell fragments and cellular dysfunction trigger inflammatory responses. Irrespective of the cause, inflammasomes are key intracellular multiprotein signaling platforms which sense neuropathological conditions. The activation of inflammasomes leads to the auto-proteolytic cleavage of caspase-1, resulting in the proteolysis of the pro-inflammatory cytokines interleukin (IL)1beta and IL18 into their bioactive forms...
May 6, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28462526/molecular-mechanisms-and-functions-of-pyroptosis-inflammatory-caspases-and-inflammasomes-in-infectious-diseases
#8
REVIEW
Si Ming Man, Rajendra Karki, Thirumala-Devi Kanneganti
Cell death is a fundamental biological phenomenon that is essential for the survival and development of an organism. Emerging evidence also indicates that cell death contributes to immune defense against infectious diseases. Pyroptosis is a form of inflammatory programmed cell death pathway activated by human and mouse caspase-1, human caspase-4 and caspase-5, or mouse caspase-11. These inflammatory caspases are used by the host to control bacterial, viral, fungal, or protozoan pathogens. Pyroptosis requires cleavage and activation of the pore-forming effector protein gasdermin D by inflammatory caspases...
May 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28459430/chemotherapy-drugs-induce-pyroptosis-through-caspase-3-cleavage-of-a-gasdermin
#9
Yupeng Wang, Wenqing Gao, Xuyan Shi, Jingjin Ding, Wang Liu, Huabin He, Kun Wang, Feng Shao
Pyroptosis, activated by the canonical caspase-1 inflammasomes or caspase-4/5/11 by cytosolic LPS, is critical for immunity(1,2,3). The caspases cleave Gasdermin D (GSDMD) in the middle linker to release autoinhibition on its Gasdermin-N domain that executes pyroptosis via the pore-forming activity(4,5,6,7,8,9). GSDMD belongs to a Gasdermin family sharing the pore-forming domain(4,6,10). The function and mechanism of activation for other Gasdermins are unknown. Here we show that GSDME, originally identified as DFNA5 (Deafness, Autosomal Dominant 5)(11), could switch TNFα or chemotherapy drugs-induced and caspase-3-mediated apoptosis to pyroptosis...
May 1, 2017: Nature
https://www.readbyqxmd.com/read/28452921/targeting-circulating-leukocytes-and-pyroptosis-during-ex-vivo-lung-perfusion-improves-lung-preservation
#10
Kentaro Noda, Shinya Tane, Seok Jin Haam, Jonathan D'Cunha, Awori J Hayanga, James D Luketich, Norihisa Shigemura
BACKGROUND: The role of the circulating leukocytes in lungs and their relationship with circulating proinflammatory cytokines during ischemia-reperfusion injury is not well understood. Using ex vivo lung perfusion (EVLP) to investigate the pathophysiology of isolated lungs, we aimed to identify a therapeutic target to optimize lung preservation leading to successful lung transplantation. METHODS: Rat heart-lung blocks were placed on EVLP for 4 hours with or without a leukocyte-depleting filter (LF)...
April 27, 2017: Transplantation
https://www.readbyqxmd.com/read/28436935/tnf-superfamily-receptor-ox40-triggers-invariant-nkt-cell-pyroptosis-and-liver-injury
#11
Peixiang Lan, Yihui Fan, Yue Zhao, Xiaohua Lou, Howard P Monsour, Xiaolong Zhang, Yongwon Choi, Yaling Dou, Naoto Ishii, Rafik M Ghobrial, Xiang Xiao, Xian Chang Li
Tissue-resident immune cells play a key role in local and systemic immune responses. The liver, in particular, hosts a large number of invariant natural killer T (iNKT) cells, which are involved in diverse immune responses. However, the mechanisms that regulate survival and homeostasis of liver iNKT cells are poorly defined. Here we have found that liver iNKT cells constitutively express the costimulatory TNF superfamily receptor OX40 and that OX40 stimulation results in massive pyroptotic death of iNKT cells, characterized by the release of potent proinflammatory cytokines that induce liver injury...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28415686/chikusetsu-saponin-iva-ameliorates-high-fat-diet-induced-inflammation-in-adipose-tissue-of-mice-through-inhibition-of-nlrp3-inflammasome-activation-and-nf-%C3%AE%C2%BAb-signaling
#12
Chengfu Yuan, Chaoqi Liu, Ting Wang, Yumin He, Zhiyong Zhou, Yaoyan Dun, Haixia Zhao, Dongming Ren, Junjie Wang, Changcheng Zhang, Ding Yuan
Chronic metabolic inflammation in adipose tissue plays an important role in the development of obesity-associated diseases. Our previous study indicated that total saponins of Panax japonicus (SPJ) rhizoma and Chikusetsu saponin V, one main component of SPJ, could exert the anti-oxidative and anti-inflammatory effects. The present study aimed to investigate the in vivo and Ex vivo anti-inflammatory activities of another main component of SPJ, namely Chikusetsu saponin IVa (CS). CS could significantly inhibited HFD-induced lipid homeostasis, and inhibited inflammation in adipose tissue, as reflected by the decreased mRNA expression levels of inflammation-related genes and secretion of the chemokines/cytokines, inhibited the accumulation of adipose tissue macrophages (ATMs) and shifted their polarization from M1 to M2, suppressed HFD-induced expression of NLRP3 inflammasome component genes and decreased IL-1β and Caspase-1 production in mice...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398673/melatonin-alleviates-inflammasome-induced-pyroptosis-through-inhibiting-nf-%C3%AE%C2%BAb-gsdmd-signal-in-mice-adipose-tissue
#13
Zhenjiang Liu, Lu Gan, Yatao Xu, Dan Luo, Qian Ren, Song Wu, Chao Sun
Pyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti-inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome-induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)-induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome-mediated pyroptosis was also inhibited by melatonin in adipocytes...
April 11, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28392147/pyroptosis-and-apoptosis-pathways-engage-in-bidirectional-crosstalk-in-monocytes-and-macrophages
#14
Cornelius Y Taabazuing, Marian C Okondo, Daniel A Bachovchin
Pyroptosis is a lytic form of programmed cell death mediated by the inflammatory caspase-1, -4, and -5. We recently discovered that small-molecule inhibitors of the serine peptidases DPP8 and DPP9 (DPP8/9) induce pro-caspase-1-dependent pyroptosis in monocytes and macrophages. Notably, DPP8/9 inhibitors, unlike microbial agents, absolutely require caspase-1 to induce cell death. Therefore, DPP8/9 inhibitors are useful probes to study caspase-1 in cells. Here, we show that, in the absence of the pyroptosis-mediating substrate gasdermin D (GSDMD), caspase-1 activates caspase-3 and -7 and induces apoptosis, demonstrating that GSDMD is the only caspase-1 substrate that induces pyroptosis...
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28381300/linkages-between-changes-in-the-3d-organization-of-the-genome-and-transcription-during-myotube-differentiation-in-vitro
#15
Malina D Doynova, James F Markworth, David Cameron-Smith, Mark H Vickers, Justin M O'Sullivan
BACKGROUND: The spatial organization of eukaryotic genomes facilitates and reflects the underlying nuclear processes that are occurring in the cell. As such, the spatial organization of a genome represents a window on the genome biology that enables analysis of the nuclear regulatory processes that contribute to mammalian development. METHODS: In this study, Hi-C and RNA-seq were used to capture the genome organization and transcriptome in mouse muscle progenitor cells (C2C12 myoblasts) before and after differentiation to myotubes, in the presence or absence of the cytidine analogue AraC...
April 5, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28369745/inflammasome-gene-profile-is-modulated-in-septic-patients-with-a-greater-magnitude-in-non-survivors
#16
K F Esquerdo, N K Sharma, M K C Brunialti, G L Baggio-Zappia, M Assunção, L C P Azevedo, A T Bafi, R Salomao
Inflammasome signalling induces the processing and secretion of interleukin (IL)-1β and IL-18 which, coupled with pyroptosis, activate further the inflammatory response. In the present study we evaluated the expression of genes involved in inflammasome signalling pathways in septic patients, their interaction networks and the predicted functions modulated in survivors and non-survivors. Twenty-seven patients with sepsis secondary to community-acquired pneumonia admitted to intensive care units from three general hospitals in São Paulo were included into the study...
April 2, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28362726/-hints-in-the-killer-protein-gasdermin-d-unveiling-the-secrets-of-gasdermins-driving-cell-death
#17
REVIEW
Shiqiao Qiu, Jing Liu, Feiyue Xing
Pyroptosis is a lytic form of cell death distinguished from apoptosis, ferroptosis, necrosis, necroptosis, NETosis, oncosis, pyronecrosis and autophagy. Proinflammatory caspases cleave a gasdermin D (GSDMD) protein to generate a 31 kDa N-terminal domain. The cleavage relieves the intramolecular inhibition on the gasdermin-N domain, which then moves to the plasma membrane to exhibit pore-forming activity. Thus, GSDMD acts as the final and direct executor of pyroptotic cell death. Owing to the selective targeting of the inner leaflet of the plasma membrane with the pore-forming that determines pyroptotic cell death, GSDMD could be a potential target to control cell death or extracellular bacterial infections...
April 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28360909/inflammasomes-in-inflammation-induced-cancer
#18
REVIEW
Chu Lin, Jun Zhang
The inflammasome is an important multiprotein complex that functions during inflammatory immune responses. The activation of inflammasome will lead to the autoactivation of caspase-1 and subsequent cleavage of proIL-1β and proIL-18, which are key sources of inflammatory manifestations. Recently, the roles of inflammasomes in cancers have been extensively explored, especially in inflammation-induced cancers. In different and specific contexts, inflammasomes exhibit distinct and even contrasting effects in cancer development...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28345767/nlrp3-inflammasome-its-regulation-and-involvement-in-atherosclerosis
#19
REVIEW
Zahra Hoseini, Fatemeh Sepahvand, Bahman Rashidi, Amirhossein Sahebkar, Aria Masoudifar, Hamed Mirzaei
Inflammasomes are intracellular complexes involved in the innate immunity that convert proIL-1β and proIL-18 to mature forms and initiate pyroptosis via cleaving procaspase-1. The most well-known inflammasome is NLRP3. Several studies have indicated a decisive and important role of NLRP3 inflammasome, IL-1β, IL-18, and pyroptosis in atherosclerosis. Modern hypotheses introduce atherosclerosis as an inflammatory/lipid-based disease and NLRP3 inflammasome has been considered as a link between lipid metabolism and inflammation because crystalline cholesterol and oxidized low-density lipoprotein (oxLDL) (two abundant components in atherosclerotic plaques) activate NLRP3 inflammasome...
March 27, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28345580/differential-roles-of-caspase-1-and-caspase-11-in-infection-and-inflammation
#20
Si Ming Man, Rajendra Karki, Benoit Briard, Amanda Burton, Sebastien Gingras, Stephane Pelletier, Thirumala-Devi Kanneganti
Caspase-1, also known as interleukin-1β (IL-1β)-converting enzyme (ICE), regulates antimicrobial host defense, tissue repair, tumorigenesis, metabolism and membrane biogenesis. On activation within an inflammasome complex, caspase-1 induces pyroptosis and converts pro-IL-1β and pro-IL-18 into their biologically active forms. "ICE(-/-)" or "Casp1(-/-)" mice generated using 129 embryonic stem cells carry a 129-associated inactivating passenger mutation on the caspase-11 locus, essentially making them deficient in both caspase-1 and caspase-11...
March 27, 2017: Scientific Reports
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