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Sara Crespo Yanguas, Joost Willebrords, Scott R Johnstone, Michaël Maes, Elke Decrock, Marijke De Bock, Luc Leybaert, Bruno Cogliati, Mathieu Vinken
Pannexins form channels at the plasma membrane surface that establish a pathway for communication between the cytosol of individual cells and their extracellular environment. By doing so, pannexin signaling dictates several physiological functions, but equally underlies a number of pathological processes. Indeed, pannexin channels drive inflammation by assisting in the activation of inflammasomes, the release of pro-inflammatory cytokines, and the activation and migration of leukocytes. Furthermore, these cellular pores facilitate cell death, including apoptosis, pyroptosis and autophagy...
October 11, 2016: Biochimica et Biophysica Acta
Ashley A Basiorka, Kathy L McGraw, Erika A Eksioglu, Xianghong Chen, Joseph Johnson, Ling Zhang, Qing Zhang, Brittany A Irvine, Thomas Cluzeau, David A Sallman, Eric Padron, Rami Komrokji, Lubomir Sokol, Rebecca C Coll, Avril A B Robertson, Matthew A Cooper, John L Cleveland, Luke A O'Neill, Sheng Wei, Alan F List
Despite genetic heterogeneity, myelodysplastic syndromes (MDS) share features of cytological dysplasia and ineffective hematopoiesis. We report that a hallmark of MDS is activation of the NLRP3 inflammasome, which drives clonal expansion and pyroptotic cell death. Independent of genotype, MDS hematopoietic stem/progenitor cells (HSPC) overexpress inflammasome proteins and manifest activated NLRP3 complexes that direct activation of caspase-1, generation of IL-1β and IL-18 and pyroptotic cell death. Mechanistically, pyroptosis is triggered by the alarmin S100A9 that is found in excess in MDS HSPC and bone marrow plasma...
October 13, 2016: Blood
Laura Schoenlaub, Rama Cherla, Yan Zhang, Guoquan Zhang
Our recent study demonstrated that virulent Coxiella burnetii Nine Mile phase I (NMI) is capable of infecting and replicating within peritoneal B1a cells and that B1a cells play an important role in host defense against C. burnetii infection in mice. However, it remains unknown if avirulent Nine Mile phase II (NMII) can infect and replicate in B1a cells and whether NMI and NMII can differentially interact with B1a cells. In this study, we examined if NMI and NMII can differentially modulate host cell apoptotic signaling in B1a cells...
October 10, 2016: Infection and Immunity
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...
October 11, 2016: Stem Cells Translational Medicine
Qun Chu, Yanan Jiang, Wei Zhang, Chaoqian Xu, Weijie Du, Gulnara Tuguzbaeva, Ying Qin, Anqi Li, Liangshuan Zhang, Guiyuan Sun, Yongqiao Cai, Qiang Feng, Guiyang Li, Yanyao Li, Zhimin Du, Yunlong Bai, Baofeng Yang
Pyroptosis is a caspase-1 dependent programmed cell death, which is involved in the pathologic process of several kinds of cancers. Loss of caspase-1 gene expression has been observed in prostate and gastric cancers. However, the role of pyroptosis in human hepatocellular carcinoma (HCC) remains largely unknown. The aim of this study was to investigate the involvement of pyroptosis in the pathogenesis of HCC. Our study showed that pyroptosis was inhibited in HCC tissues and cells. Administration of berberine inhibited the viability, migration and invasion capacity of HepG2 cells through the induction of pyroptosis both in vitro and in vivo, which was attenuated by caspase-1 inhibitor Ac-YVAD-CMK...
October 1, 2016: Oncotarget
Gaurav Shrivastava, Moisés León-Juárez, Julio García-Cordero, David Eduardo Meza-Sánchez, Leticia Cedillo-Barrón
A complex interplay between pathogen and host determines the immune response during viral infection. A set of cytosolic sensors are expressed by immune cells to detect viral infection. NOD-like receptors (NLRs) comprise a large family of intracellular pattern recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed inflammasomes, which induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3 or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), and the effector protein procaspase-1...
October 3, 2016: Immunologic Research
Brooke A Napier, Sky W Brubaker, Timothy E Sweeney, Patrick Monette, Greggory H Rothmeier, Nina A Gertsvolf, Andreas Puschnik, Jan E Carette, Purvesh Khatri, Denise M Monack
Cell death and release of proinflammatory mediators contribute to mortality during sepsis. Specifically, caspase-11-dependent cell death contributes to pathology and decreases in survival time in sepsis models. Priming of the host cell, through TLR4 and interferon receptors, induces caspase-11 expression, and cytosolic LPS directly stimulates caspase-11 activation, promoting the release of proinflammatory cytokines through pyroptosis and caspase-1 activation. Using a CRISPR-Cas9-mediated genome-wide screen, we identified novel mediators of caspase-11-dependent cell death...
October 3, 2016: Journal of Experimental Medicine
Virginie Deswaerte, Saleela M Ruwanpura, Brendan J Jenkins
Over the last decade it has emerged that inflammasome complexes provide a pivotal platform for the host innate immune system to respond to exogenous infectious microbes (viruses, bacteria, fungi) and non-infectious environmental agents (cigarette smoke, pollution), as well as endogenous "danger" signals. Upon the canonical activation of inflammasomes, a key effector function is to catalyze, via caspase-1, the maturation of the potent pro-inflammatory cytokines interleukin (IL)-1β and IL-18, which, in addition to chronic inflammatory responses have also been intimately linked to the inflammatory form of lytic cell death, pyroptosis...
September 30, 2016: Molecular Immunology
Si Ming Man, Rajendra Karki, Miwa Sasai, David E Place, Sannula Kesavardhana, Jamshid Temirov, Sharon Frase, Qifan Zhu, R K Subbarao Malireddi, Teneema Kuriakose, Jennifer L Peters, Geoffrey Neale, Scott A Brown, Masahiro Yamamoto, Thirumala-Devi Kanneganti
The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of caspase-1, pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes; however, the mechanisms by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria...
October 6, 2016: Cell
Ine Jorgensen, Joseph P Lopez, Stefan A Laufer, Edward A Miao
Inflammasomes activate caspase-1, initiating a lytic form of programmed cell death termed pyroptosis, which is an important innate immune defense mechanism against intracellular infections. We recently demonstrated in a mouse infection model of pyroptosis that instead of releasing bacteria into the extracellular space, bacteria remain trapped within the pyroptotic cell corpse, termed the pore-induced intracellular trap (PIT). This trapping mediates efferocytosis of the PIT, with its associated bacteria, by neutrophils; bacteria are subsequently killed via neutrophil ROS...
September 28, 2016: European Journal of Immunology
Yuan He, Hideki Hara, Gabriel Núñez
Members of the nucleotide-binding domain and leucine-rich repeat (LRR)-containing (NLR) family and the pyrin and HIN domain (PYHIN) family can form multiprotein complexes termed 'inflammasomes'. The biochemical function of inflammasomes is to activate caspase-1, which leads to the maturation of interleukin 1 beta (IL-1β) and IL-18 and the induction of pyroptosis, a form of cell death. Unlike other inflammasomes, the NLRP3 inflammasome can be activated by diverse stimuli. The importance of the NLRP3 inflammasome in immunity and human diseases has been well documented, but the mechanism and regulation of its activation remain unclear...
September 23, 2016: Trends in Biochemical Sciences
Karsten Eichholz, Thierry Bru, Thi Thu Phuong Tran, Paulo Fernandes, Hugh Welles, Franck J D Mennechet, Nicolas Manel, Paula Alves, Matthieu Perreau, Eric J Kremer
Human adenoviruses (HAdVs) are nonenveloped proteinaceous particles containing a linear double-stranded DNA genome. HAdVs cause a spectrum of pathologies in all populations regardless of health standards. Following repeat exposure to multiple HAdV types, we develop robust and long-lived humoral and cellular immune responses that provide life-long protection from de novo infections and persistent HAdV. How HAdVs, anti-HAdV antibodies and antigen presenting cells (APCs) interact to influence infection is still incompletely understood...
September 2016: PLoS Pathogens
Dan Zhao, Yaqin Wu, Jiabao Zhuang, Chun Xu, Fuqiang Zhang
Inflammasomes have been reported to be present in periodontal inflammatory tissue, but the exact role of inflammasomes in periodontal inflammatory reactions especially those related to mechanical stimulations has not been clarified. In this study, it was shown that cyclic stretch activated the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 1 and 3 (NLRP1 and NLRP3) inflammasomes and induced the release of IL-1β and pyroptosis via a caspase-1-related mechanism in human periodontal ligament cells (HPDLCs)...
September 10, 2016: Oncotarget
Nicolas J Pillon, Kenny L Chan, Shitian Zhang, Marios Mejdani, Maya R Jacobson, Alexandre Ducos, Philip J Bilan, Wenyan Niu, Amira Klip
Obesity is associated with metabolic tissue infiltration by monocyte-derived macrophages. Saturated fatty acids contribute to pro-inflammatory gene induction in tissue-embedded immune cells. However, it is unknown how circulating monocytes -the macrophage precursors- react to high fat environments. In macrophages, saturated fatty acids activate inflammatory pathways and, notably, prime caspase-associated inflammasomes. Inflammasome-activated IL1β contributes to type 2 diabetes. We hypothesized that a) human monocytes from obese patients show caspase activation, and b) fatty acids trigger this response and consequent release of IL1β/IL18...
September 13, 2016: American Journal of Physiology. Endocrinology and Metabolism
Saverio Cinti
In all mammals, adipocytes are cells with abundant cytoplasmic lipids forming the parenchyma of the adipose organ. White adipocytes store highly energetic molecules to release them, in the form of free fatty acids to survive between meals. Brown adipocytes trough their unique mitochondrial UCP1 protein burn glucose and lipids to perform thermogenesis in order to survive in cold environments. A third type of adipocytes appears in the subcutaneous depot of the adipose organ of female mice during pregnancy and lactation: the pink adipocytes...
September 10, 2016: Biochimie
Motoko Sasaki, Yasuni Nakanuma
Various cellular responses including apoptosis, necrosis, autophagy and cellular senescence are involved in the pathogenesis of inflammatory cholangiopathies, such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and biliary atresia (BA). For example, dysregulated autophagy may play a role in abnormal expression of mitochondrial antigens and following autoimmune pathogenesis in bile duct lesions in PBC. Recently, new types of regulated cell death including necroptosis, parthanatos, pyroptosis, immunogenic cell death are the subject of numerous reports and they may play roles in pathogenesis of liver diseases, such as nonalcoholic steatohepatitis...
September 8, 2016: Clinics and Research in Hepatology and Gastroenterology
Jie Yang, Yanfeng Zhao, Peng Zhang, Yuehua Li, Yong Yang, Yang Yang, Junjie Zhu, Xiao Song, Gening Jiang, Jie Fan
Hemorrhagic shock (HS) often renders patients more susceptible to lung injury by priming for an exaggerated response to a second infectious stimulus. Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome following HS and regularly serves as a major cause of patient mortality. The lung vascular endothelium is an active organ that has a central role in the development of ALI through synthesizing and releasing of a number of inflammatory mediators. Cell pyroptosis is a caspase-1-dependent regulated cell death, which features rapid plasma membrane rupture and release of proinflammatory intracellular contents...
2016: Cell Death & Disease
Huanhuan Liang, Yingfang Liu
No abstract text is available yet for this article.
October 2016: Science China. Life Sciences
Mathieu Heulot, Nadja Chevalier, Julien Puyal, Christiane Margue, Sébastien Michel, Stephanie Kreis, Dagmar Kulms, David Barras, Aimable Nahimana, Christian Widmann
Tumor cell resistance to apoptosis, which is triggered by many anti-tumor therapies, remains a major clinical problem. Therefore, development of more efficient therapies is a priority to improve cancer prognosis. We have previously shown that a cell-permeable peptide derived from the p120 Ras GTPase-activating protein (RasGAP), called TAT-RasGAP317-326, bears anti-malignant activities in vitro and in vivo, such as inhibition of metastatic progression and tumor cell sensitization to cell death induced by various anti-cancer treatments...
September 2, 2016: Oncotarget
Christopher Lupfer, Paras K Anand
Inflammasomes are cytosolic multiprotein platforms with pivotal roles in infectious diseases. Activation of inflammasomes results in proinflammatory cytokine signaling and pyroptosis. Sexually transmitted infections (STIs) are a major health problem worldwide, yet few studies have probed the impact of inflammasome signaling during these infections. Due to the dearth of appropriate infection models, our current understanding of inflammasomes in STIs is mostly drawn from results obtained in vitro, from distant infection sites, or from related microbial strains that are not sexually transmitted...
October 2016: Trends in Immunology
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