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https://www.readbyqxmd.com/read/28436935/tnf-superfamily-receptor-ox40-triggers-invariant-nkt-cell-pyroptosis-and-liver-injury
#1
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
#2
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...
March 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28329768/corrigendum-cell-death-by-pyroptosis-drives-cd4-t-cell-depletion-in-hiv-1-infection
#11
Gilad Doitsh, Nicole L K Galloway, Xin Geng, Zhiyuan Yang, Kathryn M Monroe, Orlando Zepeda, Peter W Hunt, Hiroyu Hatano, Stefanie Sowinski, Isa Muñoz-Arias, Warner C Greene
No abstract text is available yet for this article.
April 6, 2017: Nature
https://www.readbyqxmd.com/read/28297565/rationale-for-determining-the-functional-potency-of-mesenchymal-stem-cells-in-preventing-regulated-cell-death-for-therapeutic-use
#12
Abderrahim Naji, Narufumi Suganuma, Nicolas Espagnolle, Ken-Ichi Yagyu, Nobuyasu Baba, Luc Sensebé, Frédéric Deschaseaux
Mesenchymal stem (stromal) cells (MSCs) are being investigated for treating degenerative and inflammatory disorders because of their reparative and immunomodulatory properties. Intricate mechanisms relate cell death processes with immune responses, which have implications for degenerative and inflammatory conditions. We review the therapeutic value of MSCs in terms of preventing regulated cell death (RCD). When cells identify an insult, specific intracellular pathways are elicited for execution of RCD processes, such as apoptosis, necroptosis, and pyroptosis...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28280602/impact-of-caspase-1-11-3-7-or-il-1%C3%AE-il-18-deficiency-on-rabies-virus-induced-macrophage-cell-death-and-onset-of-disease
#13
E Kip, F Nazé, V Suin, T Vanden Berghe, A Francart, S Lamoral, P Vandenabeele, R Beyaert, S Van Gucht, M Kalai
Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: Challenge Virus Standard strain-11 (CVS-11) is highly neurotropic and lethal for mice, while the attenuated Evelyn-Rotnycki-Abelseth (ERA) strain has a broader cell tropism, is non-lethal and has been used as an oral vaccine for animals...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28271472/the-canonical-inflammasome-a-macromolecular-complex-driving-inflammation
#14
Tom P Monie
The inflammasome is a multi-molecular platform crucial to the induction of an inflammatory response to cellular danger. Recognition in the cytoplasm of endogenously and exogenously derived ligands initiates conformational change in sensor proteins, such as NLRP3, that permits the subsequent rapid recruitment of adaptor proteins, like ASC, and the resulting assembly of a large-scale inflammatory signalling platform. The assembly process is driven by sensor-sensor interactions as well as sensor-adaptor and adaptor-adaptor interactions...
2017: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/28268194/a-bioluminescent-caspase-1-activity-assay-rapidly-monitors-inflammasome-activation-in-cells
#15
Martha O'Brien, Danielle Moehring, Raúl Muñoz-Planillo, Gabriel Núñez, Justin Callaway, Jenny Ting, Mike Scurria, Tim Ugo, Laurent Bernad, James Cali, Dan Lazar
Inflammasomes are protein complexes induced by diverse inflammatory stimuli that activate caspase-1, resulting in the processing and release of cytokines, IL-1β and IL-18, and pyroptosis, an immunogenic form of cell death. To provide a homogeneous method for detecting caspase-1 activity, we developed a bioluminescent, plate-based assay that combines a substrate, Z-WEHD-aminoluciferin, with a thermostable luciferase in an optimized lytic reagent added directly to cultured cells. Assay specificity for caspase-1 is conferred by inclusion of a proteasome inhibitor in the lytic reagent and by use of a caspase-1 inhibitor to confirm activity...
March 4, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28266511/immunity-to-uropathogens-the-emerging-roles-of-inflammasomes
#16
REVIEW
Claire Hamilton, Lionel Tan, Thomas Miethke, Paras K Anand
Urinary tract infections (UTIs) cause a huge burden of morbidity worldwide with recurrent UTIs becoming increasingly frequent owing to the emergence of antibiotic-resistant bacterial strains. Interactions between the innate and adaptive immune responses to pathogens colonizing the urinary tract have been the focus of much research. Inflammasomes are part of the innate immune defence and can respond rapidly to infectious insult. Assembly of the multiprotein inflammasome complex activates caspase-1, processes proinflammatory cytokines IL-1β and IL-18, and induces pyroptosis...
March 7, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28263976/nlrp1-promotes-tumor-growth-by-enhancing-inflammasome-activation-and-suppressing-apoptosis-in-metastatic-melanoma
#17
Z Zhai, W Liu, M Kaur, Y Luo, J Domenico, J M Samson, Y G Shellman, D A Norris, C A Dinarello, R A Spritz, M Fujita
Inflammasomes are mediators of inflammation, and constitutively activated NLRP3 inflammasomes have been linked to interleukin-1β (IL-1β)-mediated tumorigenesis in human melanoma. Whereas NLRP3 regulation of caspase-1 activation requires the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain)), caspase-1 activation by another danger-signaling sensor NLRP1 does not require ASC because NLRP1 contains a C-terminal CARD domain that facilitates direct caspase-1 activation via CARD-CARD interaction...
March 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28261564/legionella-pneumophila-strain-130b-evades-macrophage-cell-death-independent-of-the-effector-sidf-in-the-absence-of-flagellin
#18
Mary Speir, Adam Vogrin, Azadeh Seidi, Gilu Abraham, Stéphane Hunot, Qingqing Han, Gerald W Dorn, Seth L Masters, Richard A Flavell, James E Vince, Thomas Naderer
The human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. Using live-cell imaging to follow the L. pneumophila-macrophage interaction, we now demonstrate that L. pneumophila evades host cell apoptosis independent of SidF...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28258192/atg7-deficiency-intensifies-inflammasome-activation-and-pyroptosis-in-pseudomonas-sepsis
#19
Qinqin Pu, Changpei Gan, Rongpeng Li, Yi Li, Shirui Tan, Xuefeng Li, Yuquan Wei, Lefu Lan, Xin Deng, Haihua Liang, Feng Ma, Min Wu
Sepsis is a severe and complicated syndrome that is characterized by dysregulation of host inflammatory responses and organ failure, with high morbidity and mortality. The literature implies that autophagy is a crucial regulator of inflammation in sepsis. In this article, we report that autophagy-related protein 7 (Atg7) is involved in inflammasome activation in Pseudomonas aeruginosa abdominal infection. Following i.p. challenge with P. aeruginosa, atg7(fl/fl) mice showed impaired pathogen clearance, decreased survival, and widespread dissemination of bacteria into the blood and lung tissue compared with wild-type mice...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28245134/nlrp3-inflammasome-deficiency-protects-against-microbial-sepsis-via-increased-lipoxin-b4-synthesis
#20
Seonmin Lee, Kiichi Nakahira, Jesmond Dalli, Ilias I Siempos, Paul C Norris, Romain A Colas, Jong-Seok Moon, Masakazu Shinohara, Shu Hisata, Judie Ann Howrylak, Gee-Young Suh, Stefan W Ryter, Charles N Serhan, Augustine M K Choi
RATIONALE: Sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection, is a major public health concern with high mortality and morbidity. Although inflammatory responses triggered by infection are crucial for host defense against invading microbes, the excessive inflammation often causes tissue damage leading to organ dysfunction. Resolution of inflammation, an active immune process mediated by endogenous lipid mediators (LMs), is important to maintain host homeostasis...
February 28, 2017: American Journal of Respiratory and Critical Care Medicine
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