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https://www.readbyqxmd.com/read/29212904/dendritic-cell-ripk1-maintains-immune-homeostasis-by-preventing-inflammation-and-autoimmunity
#1
Joanne A O'Donnell, Jesse Lehman, Justine E Roderick, Dalia Martinez-Marin, Matija Zelic, Ciara Doran, Nicole Hermance, Stephen Lyle, Manolis Pasparakis, Katherine A Fitzgerald, Ann Marshak-Rothstein, Michelle A Kelliher
Necroptosis is a form of cell death associated with inflammation; however, the biological consequences of chronic necroptosis are unknown. Necroptosis is mediated by RIPK1, RIPK3, and MLKL kinases but in hematopoietic cells RIPK1 has anti-inflammatory roles and functions to prevent necroptosis. Here we interrogate the consequences of chronic necroptosis on immune homeostasis by deleting Ripk1 in mouse dendritic cells. We demonstrate that deregulated necroptosis results in systemic inflammation, tissue fibrosis, and autoimmunity...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29203926/pandemic-h1n1-influenza-a-viruses-suppress-immunogenic-ripk3-driven-dendritic-cell-death
#2
Boris M Hartmann, Randy A Albrecht, Elena Zaslavsky, German Nudelman, Hanna Pincas, Nada Marjanovic, Michael Schotsaert, Carles Martínez-Romero, Rafael Fenutria, Justin P Ingram, Irene Ramos, Ana Fernandez-Sesma, Siddharth Balachandran, Adolfo García-Sastre, Stuart C Sealfon
The risk of emerging pandemic influenza A viruses (IAVs) that approach the devastating 1918 strain motivates finding strain-specific host-pathogen mechanisms. During infection, dendritic cells (DC) mature into antigen-presenting cells that activate T cells, linking innate to adaptive immunity. DC infection with seasonal IAVs, but not with the 1918 and 2009 pandemic strains, induces global RNA degradation. Here, we show that DC infection with seasonal IAV causes immunogenic RIPK3-mediated cell death. Pandemic IAV suppresses this immunogenic DC cell death...
December 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/29203883/abin-1-regulates-ripk1-activation-by-linking-met1-ubiquitylation-with-lys63-deubiquitylation-in-tnf-rsc
#3
Slawomir A Dziedzic, Zhenyi Su, Vica Jean Barrett, Ayaz Najafov, Adnan K Mookhtiar, Palak Amin, Heling Pan, Li Sun, Hong Zhu, Averil Ma, Derek W Abbott, Junying Yuan
Ubiquitylation of the TNFR1 signalling complex (TNF-RSC) controls the activation of RIPK1, a kinase critically involved in mediating multiple TNFα-activated deleterious events. However, the molecular mechanism that coordinates different types of ubiquitylation modification to regulate the activation of RIPK1 kinase remains unclear. Here, we show that ABIN-1/NAF-1, a ubiquitin-binding protein, is recruited rapidly into TNF-RSC in a manner dependent on the Met1-ubiquitylating complex LUBAC to regulate the recruitment of A20 to control Lys63 deubiquitylation of RIPK1...
December 4, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29200200/wogonin-protects-against-cisplatin-induced-acute-kidney-injury-by-targeting-ripk1-mediated-necroptosis
#4
Xiao-Ming Meng, Hai-Di Li, Wei-Feng Wu, Patrick Ming-Kuen Tang, Gui-Ling Ren, Li Gao, Xiao-Feng Li, Yang Yang, Tao Xu, Tao-Tao Ma, Zeng Li, Cheng Huang, Lei Zhang, Xiong-Wen Lv, Jun Li
Acute kidney injury (AKI), characterized by aggressive inflammatory responses and destruction of renal resident cells, can cause abrupt kidney dysfunction. To date, effective therapy for AKI is lacking. In this study, we evaluated the renoprotective effect of wogonin, an herbal active compound, using a cisplatin-induced AKI mouse model. In vivo results show that wogonin substantially suppressed the increased levels of serum creatinine and blood urea nitrogen (BUN) almost to the normal level. Wogonin also attenuated tubular damage, shown by PAS staining, electron microscopy and molecular analysis of KIM-1...
December 4, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29171784/necroptosis-promotes-autophagy-dependent-upregulation-of-damp-and-results-in-immunosurveillance
#5
Sheng-Yen Lin, Sung-Yuan Hsieh, Yi-Ting Fan, Wen-Chi Wei, Pei-Wen Hsiao, Dai-Hua Tsai, Tzong-Shoon Wu, Ning-Sun Yang
Programmed necrosis, necroptosis, is considered to be a highly immunogenic activity, often mediated via the release of damage-associated molecular patterns (DAMPs). Interestingly, enhanced macroautophagic/autophagic activity is often found to be accompanied by necroptosis. However, the possible role of autophagy in the immunogenicity of necroptotic death remains largely obscure. In this study, we investigated the possible mechanistic correlation between phytochemical shikonin-induced autophagy and the shikonin-induced necroptosis for tumor immunogenicity...
November 24, 2017: Autophagy
https://www.readbyqxmd.com/read/29171448/vitamin-d-cell-death-pathways-and-tuberculosis
#6
Manik Retno Wahyunitisari, Ni Made Mertaniasih, Muhammad Amin, Wayan T Artama, Eko B Koendhori
BACKGROUND: Mycobacterium tuberculosis induces cellular necrosis that could promote spread of infection. The aim of this study is to analyze the effects of Vitamin D3 supplementation to improve the effectiveness of 2nd-line anti-tuberculosis (TB) drug therapy, especially in relation with cell death pathways. METHODS: Mus musculus C3HeB/FeJ was randomly divided into four groups containing eight animals each. The 1st group (G1), consisting of mice that were intratracheally infected with multidrug-resistant strain of M...
October 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/29170110/association-of-anti-her2-antibody-with-graphene-oxide-for-curative-treatment-of-osteosarcoma
#7
Lan Li, Chengke Luo, Zhenwei Song, Eduardo Reyes-Vargas, Fred Clayton, Jufang Huang, Peter Jensen, Xinjian Chen
The finding of HER2 overexpression in osteosarcoma (OS) makes HER2 a potential therapeutic target. However, studies indicate OS cells are nonresponsive to anti-HER2 antibody trastuzumab (TRA) therapy. We established stable, non-covalent association of TRA with nanomaterial graphene oxide (GO) to generated multivalent TRA/GO complexes that demonstrated markedly enhanced HER2-binding activity and capacity to rapidly kill OS cells. TRA/GO simultaneously induced oxidative stress and HER2 signaling in the target cells, leading to rapid depletion of the cellular inhibitors of apoptosis protein (cIAP) and caspase 8, formation of RIP1/RIPK3/MLKL necroptosome and necroptosis of the OS cells...
November 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29156831/protective-effect-of-nsa-on-intestinal-epithelial-cells-in-a-necroptosis-model
#8
Wei Dong, Min Zhang, Yaxi Zhu, Yuanhan Chen, Xingchen Zhao, Ruizhao Li, Li Zhang, Zhiming Ye, Xingling Liang
Objective: This study aimed to investigate the protective effect of the necroptosis inhibitor necrosulfonamide (NSA) on intestinal epithelial cells using a novel in vitro necroptosis model that mimics inflammatory bowel disease (IBD). Methods: 2,4,6-trinitrobenzenesulfonic acid (TNBS) was perfused into the rectum of BALB/c mice to established a colitis model. Pathologic injury and cell death were evaluated. A novel in vitro model of necroptosis was established in Caco-2 cells using TNF-α and Z-VAD-fmk, and the cells were treated with or without NSA...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29138474/phagocytosis-of-environmental-or-metabolic-crystalline-particles-induces-cytotoxicity-by-triggering-necroptosis-across-a-broad-range-of-particle-size-and-shape
#9
Mohsen Honarpisheh, Orestes Foresto-Neto, Jyaysi Desai, Stefanie Steiger, Lidia Anguiano Gómez, Bastian Popper, Peter Boor, Hans-Joachim Anders, Shrikant R Mulay
In crystallopathies, crystals or crystalline particles of environmental and metabolic origin deposit within tissues, induce inflammation, injury and cell death and eventually lead to organ-failure. The NLRP3-inflammasome is involved in mediating crystalline particles-induced inflammation, but pathways leading to cell death are still unknown. Here, we have used broad range of intrinsic and extrinsic crystal- or crystalline particle-sizes and shapes, e.g. calcium phosphate, silica, titanium dioxide, cholesterol, calcium oxalate, and monosodium urate...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137405/necroptosis-regulated-proteins-expression-is-an-early-prognostic-biomarker-in-patient-with-sepsis-a-prospective-observational-study
#10
Bing Wang, Jian Li, Hong-Mei Gao, Ying-Hong Xing, Zhu Lin, Hong-Jie Li, Yong-Qiang Wang
Background and aim: Increasing researchers indicate that necroptosis is playing an important role in the regulation of systemic inflammatory response syndrome. The current study was to investigate the prognostic biomarker of the regulated proteins of necroptosis in sepsis patients. Results: One hundred and twenty-four patients were divided into three groups: 43 patients (34.68%) with sepsis, 39 patients (31.45%) with severe sepsis, and 42 patients (33.87%) with septic shock...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29123466/neuroprotective-effect-of-%C3%AE-caryophyllene-on-cerebral-ischemia-reperfusion-injury-via-regulation-of-necroptotic-neuronal-death-and-inflammation-in-vivo-and-in-vitro
#11
Mei Yang, Yongjiu Lv, Xiaocui Tian, Jie Lou, Ruidi An, Qian Zhang, Minghang Li, Lu Xu, Zhi Dong
Necrotic cell death is a hallmark feature of ischemic stroke and it may facilitate inflammation by releasing intracellular components after cell-membrane rupture. Previous studies reported that β-caryophyllene (BCP) mitigates cerebral ischemia-reperfusion (I/R) injury, but the underlying mechanism remains unclear. We explored whether BCP exerts a neuroprotective effect in cerebral I/R injury through inhibiting necroptotic cell death and inflammation. Primary neurons with and without BCP (0.2, 1, 5, 25 μM) treatment were exposed to oxygen-glucose deprivation and re-oxygenation (OGD/R)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29104146/mlkl-pitp%C3%AE-signaling-mediated-necroptosis-contributes-to-cisplatin-triggered-cell-death-in-lung-cancer-a549-cells
#12
Lin Jing, Fei Song, Zhenyu Liu, Jianghua Li, Bo Wu, Zhiguang Fu, Jianli Jiang, Zhinan Chen
Necroptosis has been reported to be involved in cisplatin-induced cell death, but the mechanisms underlying the occurrence of necroptosis are not fully elucidated. In this study, we show that apart from apoptosis, cisplatin induces necroptosis in A549 cells. The alleviation of cell death by two necroptosis inhibitors-necrostatin-1 (Nec-1) and necrosulfonamide (NSA), and the phosphorylation of mixed lineage kinase domain-like protein (MLKL) at serine 358, suggest the involvement of receptor-interacting protein kinase 1 (RIPK1)-RIPK3-MLKL signaling in cisplatin-treated A549 cells...
November 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29103102/combination-of-emricasan-with-ponatinib-synergistically-reduces-ischemia-reperfusion-injury-in-rat-brain-through-simultaneous-prevention-of-apoptosis-and-necroptosis
#13
Jing Tian, Shu Guo, Heng Chen, Jing-Jie Peng, Miao-Miao Jia, Nian-Sheng Li, Xiao-Jie Zhang, Jie Yang, Xiu-Ju Luo, Jun Peng
Apoptosis and receptor-interacting protein kinase 1/3(RIPK1/3)-mediated necroptosis contribute to the cerebral ischemia/reperfusion (I/R) injury. Emricasan is an inhibitor of caspases in clinical trials for liver diseases while ponatinib could be a potential inhibitor for RIPK1/3. This study aims to investigate the effect of emricasan and/or ponatinib on cerebral I/R injury and the underlying mechanisms. Firstly, we evaluated the status of apoptosis and necroposis in a rat model of cerebral I/R under different conditions, which showed noticeable apoptosis and necroptosis under condition of 2-h ischemia and 24-h reperfusion; next, the preventive or therapeutic effect of emricasan or ponatinib on cerebral I/R injury was tested...
November 4, 2017: Translational Stroke Research
https://www.readbyqxmd.com/read/29101355/particles-of-different-sizes-and-shapes-induce-neutrophil-necroptosis-followed-by-the-release-of-neutrophil-extracellular-trap-like-chromatin
#14
Jyaysi Desai, Orestes Foresto-Neto, Mohsen Honarpisheh, Stefanie Steiger, Daigo Nakazawa, Bastian Popper, Eva Miriam Buhl, Peter Boor, Shrikant R Mulay, Hans-Joachim Anders
The human body is exposed to a wide range of particles of industrial, environmental or internal origin such as asbestos, alum, silica or crystals of urate, calcium phosphate, calcium oxalate, cystine or cholesterol. Phagocytic clearance of such particles involves neutrophils and macrophages. Here we report that neutrophils encountering such particles of diverse sizes and shapes undergo necrotic cell death, a process associated with the formation of neutrophil extracellular trap (NET)-like extracellular DNA...
November 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29100888/caspase-1-is-an-apical-caspase-leading-to-caspase-3-cleavage-in-the-aim2-inflammasome-response-independent-of-caspase-8
#15
Vitaliya Sagulenko, Nazarii Vitak, Parimala Vajjhala, James E Vince, Katryn J Stacey
Canonical inflammasomes are multiprotein complexes that can activate both caspase-1 and caspase-8. Caspase-1 drives rapid lysis of cells by pyroptosis and maturation of IL-1β and IL-18. In caspase-1-deficient cells, inflammasome formation still leads to caspase-3 activation and slower apoptotic death, dependent on caspase-8 as an apical caspase. A role for caspase-8 directly upstream of caspase-1 has also been suggested, but here we show that caspase-8-deficient macrophages have no defect in AIM2 inflammasome-mediated caspase-1 activation, pyroptosis and IL-1β release...
October 31, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29098922/overexpression-of-u1-snrna-induces-decrease-of-u1-spliceosome-function-associated-with-alzheimer-s-disease
#16
Zhi Cheng, Yingchun Shang, Shan Gao, Tao Zhang
We recently reported that presenilin-1 (PS1) induced an increase of U1 snRNA expression accompanied with the change of amyloid precursor protein expression, β-amyloid level and cell death. In the present study, our data showed that both overexpression and knockdown of U1 snRNA could cause the loss in the function of U1 snRNA and resulted in PCPA as well as the same downstream phenomena including the expression changes of genes specific to AD, tau hyperphosphorylation on the site of Thr212, the decrease of acetylated α-tubulin, the reduction of cell viability and upregulation of RIPK1, RIPK3 and caspase8...
November 3, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/29078411/peli1-functions-as-a-dual-modulator-of-necroptosis-and-apoptosis-by-regulating-ubiquitination-of-ripk1-and-mrna-levels-of-c-flip
#17
Huibing Wang, Huyan Meng, Xingyan Li, Kezhou Zhu, Kangyun Dong, Adnan K Mookhtiar, Huiting Wei, Ying Li, Shao-Cong Sun, Junying Yuan
Apoptosis and necroptosis are two distinct cell death mechanisms that may be activated in cells on stimulation by TNFα. It is still unclear, however, how apoptosis and necroptosis may be differentially regulated. Here we screened for E3 ubiquitin ligases that could mediate necroptosis. We found that deficiency of Pellino 1 (PELI1), an E3 ubiquitin ligase, blocked necroptosis. We show that PELI1 mediates K63 ubiquitination on K115 of RIPK1 in a kinase-dependent manner during necroptosis. Ubiquitination of RIPK1 by PELI1 promotes the formation of necrosome and execution of necroptosis...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073079/inhibition-of-dai-dependent-necroptosis-by-the-z-dna-binding-domain-of-the-vaccinia-virus-innate-immune-evasion-protein-e3
#18
Heather Koehler, Samantha Cotsmire, Jeffrey Langland, Karen V Kibler, Daniel Kalman, Jason W Upton, Edward S Mocarski, Bertram L Jacobs
Vaccinia virus (VACV) encodes an innate immune evasion protein, E3, which contains an N-terminal Z-nucleic acid binding (Zα) domain that is critical for pathogenicity in mice. Here we demonstrate that the N terminus of E3 is necessary to inhibit an IFN-primed virus-induced necroptosis. VACV deleted of the Zα domain of E3 (VACV-E3LΔ83N) induced rapid RIPK3-dependent cell death in IFN-treated L929 cells. Cell death was inhibited by the RIPK3 inhibitor, GSK872, and infection with this mutant virus led to phosphorylation and aggregation of MLKL, the executioner of necroptosis...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29042502/lipopolysaccharide-from-crypt-specific-core-microbiota-modulates-the-colonic-epithelial-proliferation-to-differentiation-balance
#19
Tomoaki Naito, Céline Mulet, Cristina De Castro, Antonio Molinaro, Azadeh Saffarian, Giulia Nigro, Marion Bérard, Mélanie Clerc, Amy B Pedersen, Philippe J Sansonetti, Thierry Pédron
We identified a crypt-specific core microbiota (CSCM) dominated by strictly aerobic, nonfermentative bacteria in murine cecal and proximal colonic (PC) crypts and hypothesized that, among its possible functions, it may affect epithelial regeneration. In the present work, we isolated representative CSCM strains using selective media based upon our initial 16S rRNA-based molecular identification (i.e., Acinetobacter, Delftia, and Stenotrophomonas). Their tropism for the crypt was confirmed, and their influence on epithelial regeneration was demonstrated in vivo by monocolonization of germfree mice...
October 17, 2017: MBio
https://www.readbyqxmd.com/read/29018243/6e11-a-highly-selective-inhibitor-of-receptor-interacting-protein-kinase-1-protects-cells-against-cold-hypoxia-reoxygenation-injury
#20
C Delehouzé, S Leverrier-Penna, F Le Cann, A Comte, M Jacquard-Fevai, O Delalande, N Desban, B Baratte, I Gallais, F Faurez, M C Bonnet, M Hauteville, P G Goekjian, R Thuillier, F Favreau, P Vandenabeele, T Hauet, M T Dimanche-Boitrel, S Bach
Necroptosis is a programmed cell death pathway that has been shown to be of central pathophysiological relevance in multiple disorders (hepatitis, brain and cardiac ischemia, pancreatitis, viral infection and inflammatory diseases). Necroptosis is driven by two serine threonine kinases, RIPK1 (Receptor Interacting Protein Kinase 1) and RIPK3, and a pseudo-kinase MLKL (Mixed Lineage Kinase domain-Like) associated in a multi-protein complex called necrosome. In order to find new inhibitors for use in human therapy, a chemical library containing highly diverse chemical structures was screened using a cell-based assay...
October 10, 2017: Scientific Reports
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