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https://www.readbyqxmd.com/read/28297565/rationale-for-determining-the-functional-potency-of-mesenchymal-stem-cells-in-preventing-regulated-cell-death-for-therapeutic-use
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
March 3, 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
#9
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
https://www.readbyqxmd.com/read/28244850/mirna-214-inhibits-cellular-proliferation-and-migration-in-glioma-cells-targeting-caspase-1-involved-in-pyroptosis
#10
Zhenfeng Jiang, Lifen Yao, Hongge Ma, Panpan Xu, Zhiyan Li, Mian Guo, Jianhang Chen, Hongbo Bao, Shupei Qiao, Yufang Zhao, Jia Shen, Minwei Zhu, Carolyn Meyers, Guizhen Ma, Chuncheng Xie, Li Liu, Haiyang Wang, Wang Zhang, Qi Dong, Hong Shen, Zhiguo Lin
Pyroptosis, is a type of pro-inflammatory programmed cell death mediated by caspase-1 activity and occurs in several types of eukaryotic tumor cells, including gliomas. MicroRNAs (miRNAs), small endogenous non-coding RNAs, have demonstrated as advantageous in glioma therapy. However, whether miRNAs regulate pyroptosis in glioma remains unknown. The current study found that caspase-1 expression was substantially increased in both glioma tissues as well as the glioma cell lines, U87 and T98G, while miR-214 expression was significantly downregulated...
December 15, 2016: Oncology Research
https://www.readbyqxmd.com/read/28204973/iaps-and-cell-death
#11
John Silke, James Vince
IAPs were named as inhibitors of apoptosis, programmed cell death, but it has become apparent that they are regulators of other types of cell death too. Because they inhibit cell death in cancer cells there has been an intense interest in developing inhibitors of these proteins to induce or sensitise cancer cells to death. In this article, we will discuss the involvement of IAPs in the apoptosis, necroptosis and pyroptosis programmed cell death paradigms. All these types of cell death are intimately involved with causing or repressing inflammation and it should perhaps therefore come as no surprise that IAPs are also involved in regulating inflammation directly...
February 16, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28197335/caspase-8-not-so-silently-deadly
#12
REVIEW
Rebecca Feltham, James E Vince, Kate E Lawlor
Apoptosis is a caspase-dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3- and MLKL-driven necroptosis, and caspase-1/11-dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase-8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin-1β (IL-1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28196749/recent-insights-into-the-molecular-mechanisms-underlying-pyroptosis-and-gasdermin-family-functions
#13
REVIEW
Robin A Aglietti, Erin C Dueber
Pyroptosis is an inflammatory form of cell death that not only protects multicellular organisms from invading pathogenic bacteria and microbial infections, but can also lead to sepsis and lethal septic shock if overactivated. Here, we present an overview of recent developments within the pyroptosis field, beginning with the discovery of Gasdermin D (GSDMD) as a substrate of caspase-1 and caspase-11 upon detection of cytosolic lipopolysaccharide (LPS). Cleavage releases the N-terminal domain of GSDMD, causing it to form cytotoxic pores in the plasma membrane of cells...
February 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28192059/inflammasomes-key-mediators-of-lung-immunity
#14
Judie A Howrylak, Kiichi Nakahira
Inflammasomes are key inflammatory signaling platforms that detect microbial substances, sterile environmental insults, and molecules derived from host cells. Activation of the inflammasome promotes caspase-1-mediated secretion of proinflammatory cytokines interleukin (IL)-1β and IL-18 and pyroptosis. Recent developments in this field demonstrate the crucial role of the inflammasome in a wide range of disease models. Although inflammasomes are a crucial part of host defense mechanisms against pathogens, the exuberant immune response resulting from inflammasome activation also contributes to the development of various diseases...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28174728/necrosis-apoptosis-necroptosis-pyroptosis-it-matters-how-acinar-cells-die-during-pancreatitis
#15
EDITORIAL
Matthias Sendler, Julia Mayerle, Markus M Lerch
No abstract text is available yet for this article.
July 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28154144/gene-polymorphism-linked-to-increased-asthma-and-ibd-risk-alters-gasdermin-b-structure-a-sulfatide-and-phosphoinositide-binding-protein
#16
Kinlin L Chao, Liudmila Kulakova, Osnat Herzberg
The exact function of human gasdermin-B (GSDMB), which regulates differentiation and growth of epithelial cells, is yet to be elucidated. In human epidermal growth factor receptor 2 (HER2)-positive breast cancer, GSDMB gene amplification and protein overexpression indicate a poor response to HER2-targeted therapy. Genome-wide association studies revealed a correlation between GSDMB SNPs and an increased susceptibility to Crohn's disease, ulcerative colitis, and asthma. The N- and C-terminal domains of all gasdermins possess lipid-binding and regulatory activities, respectively...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28151471/nlrp3-inflammasome-activation-mediates-radiation-induced-pyroptosis-in-bone-marrow-derived-macrophages
#17
Yan-Gang Liu, Ji-Kuai Chen, Zi-Teng Zhang, Xiu-Juan Ma, Yong-Chun Chen, Xiu-Ming Du, Hong Liu, Ying Zong, Guo-Cai Lu
A limit to the clinical benefit of radiotherapy is not an incapacity to eliminate tumor cells but rather a limit on its capacity to do so without destroying normal tissue and inducing inflammation. Recent evidence reveals that the inflammasome is essential for mediating radiation-induced cell and tissue damage. In this study, using primary cultured bone marrow-derived macrophages (BMDM) and a mouse radiation model, we explored the role of NLRP3 inflammasome activation and the secondary pyroptosis underlying radiation-induced immune cell death...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28147281/the-atypical-ubiquitin-e2-conjugase-ube2l3-is-an-indirect-caspase-1-target-and-controls-il-1%C3%AE-secretion-by-inflammasomes
#18
Matthew J G Eldridge, Julia Sanchez-Garrido, Gil Ferreira Hoben, Philippa J Goddard, Avinash R Shenoy
Caspase-1 activation by inflammasome signaling scaffolds initiates inflammation and antimicrobial responses. Caspase-1 proteolytically converts newly induced pro-interleukin 1 beta (IL-1β) into its mature form and directs its secretion, triggering pyroptosis and release of non-substrate alarmins such as interleukin 1 alpha (IL-1α) and HMGB1. While some caspase-1 substrates involved in these events are known, the identities and roles of non-proteolytic targets remain unknown. Here, we use unbiased proteomics to show that the UBE2L3 ubiquitin conjugase is an indirect target of caspase-1...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28140444/the-nlrp3-inflammasome-contributes-to-host-protection-during-sporothrix-schenckii-infection
#19
Amanda Costa Gonçalves, Lucas Souza Ferreira, Francine Alessandra Manente, Carolina Maria Quinello Gomes de Faria, Marisa Campos Polesi, Cleverton Roberto de Andrade, Dario Simões Zamboni, Iracilda Zeppone Carlos
Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto. Pattern recognition receptors (PRRs) recognize and respond to pathogen-associated molecular patterns (PAMPs) and shape the following adaptive immune response. A family of PRRs most frequently associated with fungal recognition is the nucleotide-binding oligomerization domain-like receptor (NLR). After PAMP recognition, NLR family pyrin domain-containing 3 (NLRP3) binds to apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 to form the NLRP3 inflammasome...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28138860/preferential-pattern-of-mouse-neutrophil-cell-death-in-response-to-various-stimulants
#20
Nuttira Luehong, Juthamart Khaowmek, Kanruethai Wongsawan, Phongsakorn Chuammitri
Neutrophils undergo cell death processes once their physiological function has been fulfilled. Apoptosis, necrosis, pyroptosis, or NETosis, a unique form of cell death, could occur, depending on the type of stimulant or inhibitory intervention. We investigated whether phorbol myristate acetate (PMA) and Klebsiella pneumoniae (KP), serving as stimulants, or whether an inhibitor (cytochalasin B, CytB) could alter the morphology and gene expression pattern associated with mouse neutrophil cell death. Fluorescence microscopy, flow cytometry, and real-time PCR approaches were used to identify morphological changes, percentages of cell death, and gene expression patterns, respectively...
January 30, 2017: In Vitro Cellular & Developmental Biology. Animal
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