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https://www.readbyqxmd.com/read/29330013/a-functional-splicing-variant-associated-with-decreased-asthma-risk-abolishes-the-ability-of-gasdermin-b-gsmdb-to-induce-epithelial-cell-pyroptosis
#1
Ronald A Panganiban, Maoyun Sun, Amber Dahlin, Hae-Ryung Park, Mengyuan Kan, Blanca E Himes, Jennifer A Mitchel, Carlos Iribarren, Eric Jorgenson, Scott H Randell, Elliot Israel, Kelan Tantisira, Stephanie Shore, Jin-Ah Park, Scott T Weiss, Ann Chen Wu, Quan Lu
BACKGROUND: Genetic variants in the chromosomal region 17q21 are consistently associated with asthma. However, mechanistic studies have not yet linked any of the associated variants to a function that could influence asthma, and as a result, the identity of the asthma gene(s) remains elusive. OBJECTIVES: We sought to identify and characterize functional variants in the 17q21 locus. METHODS: We used the Exome Aggregation Consortium (ExAC) browser to identify coding (amino acid-changing) variants in the 17q21 locus...
January 9, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29329946/a-primer-on-caspase-mechanisms
#2
REVIEW
Monica Gonzalez Ramirez, Guy S Salvesen
Caspases belong to a diverse clan of proteolytic enzymes known as clan CD with highly disparate functions in cell signaling. The caspase members of this clan are only found in animals, and most of them orchestrate the demise of cells by the highly distinct regulated cell death phenotypes known as apoptosis and pyroptosis. This review looks at the mechanistic distinctions between the activity and activation mechanisms of mammalian caspases compared to other members of clan CD. We also compare and contrast the role of different caspase family members that program anti-inflammatory and pro-inflammatory cell death pathways...
January 9, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29329580/evidence-for-the-activation-of-pyroptotic-and-apoptotic-pathways-in-rpe-cells-associated-with-nlrp3-inflammasome-in-the-rodent-eye
#3
Jiangyuan Gao, Jing Z Cui, Eleanor To, Sijia Cao, Joanne A Matsubara
BACKGROUND: Age-related macular degeneration (AMD) is a devastating eye disease causing irreversible vision loss in the elderly. Retinal pigment epithelium (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell death in the late stages of the disease. However, the exact mechanisms for RPE degeneration in AMD are still unresolved. The prevailing theories consider that each cell death pathway works independently and without regulation of each other. Building upon our previous work in which we induced a short burst of inflammasome activity in vivo, we now investigate the effects of prolonged inflammasome activity on RPE cell death mechanisms in rats...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29324702/listeria-monocytogenes-the-impact-of-cell-death-on-infection-and-immunity
#4
REVIEW
Courtney E McDougal, John-Demian Sauer
Listeria monocytogenes has evolved exquisite mechanisms for invading host cells and spreading from cell-to-cell to ensure maintenance of its intracellular lifecycle. As such, it is not surprising that loss of the intracellular replication niche through induction of host cell death has significant implications on the development of disease and the subsequent immune response. Although L. monocytogenes can activate multiple pathways of host cell death, including necrosis, apoptosis, and pyroptosis, like most intracellular pathogens L...
January 11, 2018: Pathogens
https://www.readbyqxmd.com/read/29323474/caspase-1-specific-light-up-probe-with-aggregation-induced-emission-characteristics-for-inhibitor-screening-of-coumarin-originated-natural-products
#5
Hao Lin, Haitao Yang, Shuai Huang, Fujia Wang, Dong-Mei Wang, Bin Liu, Yi-Da Tang, Chong-Jing Zhang
Caspase-1 is a key player in pyroptosis and inflammation. Caspase-1 inhibition is found to be beneficial to various diseases. Coumarin-originated natural products have an anti-inflammation function, but their direct inhibition effect to caspase-1 remains unexplored. To evaluate their interactions, the widely used commercial coumarin-based probe (Ac-YVAD-AMC) is not suitable, as the background signal from coumarin-originated natural products could interfere with the screening results. Therefore, fluorescent probes using a large Stokes shift could help solve this problem...
January 11, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29317576/-protective-effect-of-taxifolin-on-h2o2-induced-%C3%A2-h9c2-cell-pyroptosis
#6
Yanqiong Ye, Xiaoli Wang, Qian Cai, Jian Zhuang, Xiaohua Tan, Wei He, Mingyi Zhao
To explore the effect of taxifolin on H2O2-induced pyroptosis in H9C2 cells and the possible mechanisms.
 Methods: The H9C2 cells was divided into 3 groups: a control group, a hydrogen peroxide (H2O2)group and a taxifolin group. The morphology of H9C2 cells was observed by inverted phase contrast microscope. The mitochondrial membrane potential was measured by JC-1 staining and flow cytometry. The alteration of the level of reactive oxygen species (ROS) was detected by specific mitochondrial probe. The protein levels of cysteinyl aspartate specific proteinase-1 (caspase-1)was determined by Western blot...
December 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29314754/downregulation-of-gsdmd-promotes-gastric-cancer-proliferation-by-regulating-cell-cycle-related-proteins
#7
Weijie Wang, Di Chen, Mingzuo Jiang, Bing Xu, Xiaowei Li, Yi Chu, Yujie Zhang, Ren Mao, Jie Liang, Daiming Fan
AIM: Pyroptosis is a lytic form of cell death that is initiated by the activation of inflammatory caspase to defend danger signals. As the substrate of inflammatory caspase, GSDMD (gasdermin D) can be cleaved to release an N-terminal fragment that binds to the lipid membrane to form a pore-like structure, which is critically required for the induction of pyroptosis. Recent studies have shown that pyroptosis is closely related to tumor biology. Here, we aimed to identify the expression and function of GSDMD in gastric cancer...
January 4, 2018: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/29302207/role-of-inflammasomes-in-inflammatory-autoimmune-rheumatic-diseases
#8
REVIEW
Young-Su Yi
Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin (IL)-1β and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and Sjögren's syndrome (SS)...
January 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29285288/synthetic-nickel-containing-superoxide-dismutase-attenuates-para-phenylenediamine-induced-bladder-dysfunction-in-rats
#9
Bing-Juin Chiang, Tien-Wen Chen, Shiu-Dong Chung, Way-Zen Lee, Chiang-Ting Chien
Para (p)-phenylenediamine and its toxic metabolites induce excess reactive oxygen species formation that results in bladder voiding dysfunction. We determined the effects of synthetic Ni-containing superoxide dismutase mimics and the role of oxidative stress in p-phenylenediamine-induced urinary bladder dysfunction. P-phenylenediamine (60 μg/kg/day) was intraperitoneally administered for 4 weeks to induce bladder injury in female Wistar rats. Synthetic Ni-containing superoxide dismutase mimics, WCT003 (1.5 mg/kg) and WCT006 (1...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29281832/the-inflammasome-drives-gsdmd-independent-secondary-pyroptosis-and-il-1-release-in-the-absence-of-caspase-1-protease-activity
#10
Katharina S Schneider, Christina J Groß, Roland F Dreier, Benedikt S Saller, Ritu Mishra, Oliver Gorka, Rosalie Heilig, Etienne Meunier, Mathias S Dick, Tamara Ćiković, Jan Sodenkamp, Guillaume Médard, Ronald Naumann, Jürgen Ruland, Bernhard Kuster, Petr Broz, Olaf Groß
Inflammasomes activate the protease caspase-1, which cleaves interleukin-1β and interleukin-18 to generate the mature cytokines and controls their secretion and a form of inflammatory cell death called pyroptosis. By generating mice expressing enzymatically inactive caspase-1C284A, we provide genetic evidence that caspase-1 protease activity is required for canonical IL-1 secretion, pyroptosis, and inflammasome-mediated immunity. In caspase-1-deficient cells, caspase-8 can be activated at the inflammasome...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29274245/the-gasdermin-d-pore-acts-as-a-conduit-for-il-1%C3%AE-secretion-in-mice
#11
Rosalie Heilig, Mathias S Dick, Lorenzo Sborgi, Etienne Meunier, Sebastian Hiller, Petr Broz
The pro-inflammatory cytokine IL-1β is well known for its role in host defense and the initiation of potent inflammatory responses. It is processed from its inactive pro-form by the inflammatory caspase-1 into its mature bioactive form, which is then released from the cell via an unconventional secretion mechanism. Recently, gasdermin-D has been identified as a new target of caspase-1. After proteolytical cleavage of gasdermin-D, the N-terminal fragment induces pyroptosis, a lytic cell death, by forming large permeability pores in the plasma membrane...
December 23, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29273476/gasdermin-d-plays-a-key-role-as-a-pyroptosis-executor-of-non-alcoholic-steatohepatitis-in-humans-and-mice
#12
Bing Xu, Mingzuo Jiang, Yi Chu, Weijie Wang, Di Chen, Xiaowei Li, Zhao Zhang, Di Zhang, Daiming Fan, Yongzhan Nie, Feng Shao, Kaichun Wu, Jie Liang
BACKGROUND & AIMS: Gasdermin D (GSDMD)-executed programmed necrosis is involved in inflammation and controls interleukin (IL)-1β release. However, the role of GSDMD in non-alcoholic steatohepatitis (NASH) remains unclear. We investigated the role of GSDMD in the pathogenesis of steatohepatitis. METHODS: Human liver tissues of non-alcoholic fatty liver disease (NAFLD) patients and control subjects were obtained to evaluate GSDMD expression. GSDMD knockout (GSDMD-/-) mice, obese db/db mice and their wild-type (WT) littermates were fed with methionine-and-choline-deficient (MCD) or control diet to induce steatohepatitis...
December 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/29262324/caspase-1-engagement-and-tlr-induced-c-flip-expression-suppress-asc-caspase-8-dependent-apoptosis-by-inflammasome-sensors-nlrp1b-and-nlrc4
#13
Nina Van Opdenbosch, Hanne Van Gorp, Maarten Verdonckt, Pedro H V Saavedra, Nathalia M de Vasconcelos, Amanda Gonçalves, Lieselotte Vande Walle, Dieter Demon, Magdalena Matusiak, Filip Van Hauwermeiren, Jinke D'Hont, Tino Hochepied, Stefan Krautwald, Thirumala-Devi Kanneganti, Mohamed Lamkanfi
The caspase activation and recruitment domain (CARD)-based inflammasome sensors NLRP1b and NLRC4 induce caspase-1-dependent pyroptosis independent of the inflammasome adaptor ASC. Here, we show that NLRP1b and NLRC4 trigger caspase-8-mediated apoptosis as an alternative cell death program in caspase-1-/- macrophages and intestinal epithelial organoids (IECs). The caspase-8 adaptor FADD was recruited to ASC specks, which served as cytosolic platforms for caspase-8 activation and NLRP1b/NLRC4-induced apoptosis...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29250536/transient-receptor-potential-melastatin-2-negatively-regulates-lps-atp-induced-caspase-1-dependent-pyroptosis-of-bone-marrow-derived-macrophage-by-modulating-ros-production
#14
Haihong Wang, Xinyi Zhou, Hui Li, Xiaowei Qian, Yan Wang, Liang Ma
Background: Pyroptosis, a new form of cell death, which has special morphological characteristics, depends on caspase-1 activation and occupies an important role in inflammatory immune diseases and ischemia-reperfusion injury. ROS is a common activator of NLR/caspase-1. Transient receptor potential melastatin 2 (TRPM2), a selective cation channel, is involved in inflammatory regulation. This study was designed to explore the role of TRPM2 in activating caspase-1 and caspase-1-dependent pyroptosis of mouse BMDMs...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29247998/the-aim2-inflammasome-sensor-of-pathogens-and-cellular-perturbations
#15
REVIEW
Jérôme Lugrin, Fabio Martinon
Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. However, AIM2 achieves specificity by detecting altered or mislocalized DNA molecules. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment such as genomic DNA released into the cytosol upon loss of nuclear envelope integrity...
January 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29247992/metabolic-regulation-of-nlrp3
#16
REVIEW
Mark M Hughes, Luke A J O'Neill
A shift in our understanding of macrophage biology has come about as a result of recent discoveries in the area of metabolic reprogramming of macrophages. The NLRP3 inflammasome drives the activation of caspase-1, leading to the production of IL-1β, IL-18, and a type of cell death termed pyroptosis. The NLRP3 inflammasome has been shown to sense metabolites such as palmitate, uric acid, and cholesterol crystals and is inhibited by ketone bodies produced during metabolic flux. The NLRP3 inflammasome has also been shown to be regulated by mitochondrial reactive oxygen species and components of glycolysis, such as Hexokinase...
January 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29245947/alv-j-infection-induces-chicken-monocyte-death-accompanied-with-the-production-of-il-1%C3%AE-and-il-18
#17
Manman Dai, Min Feng, Tingting Xie, Yuanfang Li, Zhuohao Ruan, Meiqing Shi, Ming Liao, Xiquan Zhang
Immunosuppression induced by avian leukosis virus subgroup J (ALV-J) causes serious reproduction problems and secondary infections in chickens. Given that monocytes are important precursors of immune cells including macrophages and dendritic cells, we investigated the fate of chicken monocytes after ALV-J infection. Our results indicated that most monocytes infected with ALV-J including field or laboratory strains could not successfully differentiate into macrophages due to cells death. And cells death was dependent upon viral titer and accompanied with increased IL-1β and IL-18 mRNA levels...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29234486/jnk-signaling-a-multiplexing-hub-in-programmed-cell-death
#18
REVIEW
Danny N Dhanasekaran, E Premkumar Reddy
Jun N-terminal kinases or JNKs have been shown to be involved in a wide array of signaling events underlying tumorigenesis and tumor progression. Through its interaction with a diverse set of signaling proteins and adaptors, JNKs regulate cell proliferation, invasive migration, therapy resistance, and programmed cell death. JNKs have been shown to play a role in apoptotic as well as non-apoptotic programmed cell death mechanisms including those of necroptosis, ferroptosis, pyroptosis, and autophagy. Most of the tumorigenic regulatory functions of JNKs can be related to their ability to module cell death via these programmed cell death mechanisms...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29234126/epidermal-cornification-is-preceded-by-the-expression-of-a-keratinocyte-specific-set-of-pyroptosis-related-genes
#19
Julia Lachner, Veronika Mlitz, Erwin Tschachler, Leopold Eckhart
The homeostasis of the epidermis depends on keratinocyte differentiation and cornification, a mode of programmed cell death that does not elicit inflammation. Here, we report that cornification is associated with the expression of specific genes that control multiple steps of pyroptosis, another form of cell death that involves the processing and release of interleukin-1 family (IL1F) cytokines. Expression levels of pro-inflammatory IL1A and IL1B and of the pyroptotic pore-forming gasdermin (GSDM) D were downregulated during terminal differentiation of human keratinocytes in vitro...
December 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29229673/lncrna-gas5-suppresses-ovarian-cancer-by-inducing-inflammasome-formation
#20
Jie Li, Chen Yang, Yinguang Li, Aiyue Chen, Li Li, Zeshan You
OBJECTIVE: Long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is involved in various kinds of cancer. However, the role of lncGAS5 in the development of ovarian cancer remains unclear. In the current study, we explored the cellular mechanism and clinical value of lncRNA GAS5 in ovarian cancer. METHODS: Quantitative real-time PCR was used to detect mRNA level of LncRNA GAS5 in 20 ovarian cancer tissues. The effect of lncRNA GAS5 on cell proliferation was performed using CCK-8 assay...
December 11, 2017: Bioscience Reports
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