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https://www.readbyqxmd.com/read/28735646/hyperhomocysteinemia-and-age-related-macular-degeneration-role-of-inflammatory-mediators-and-pyroptosis-a-proposal
#1
Mahavir Singh, Suresh C Tyagi
Age-related macular degeneration (AMD) and pyroptosis cause irreversible vascular changes in the eyes leading to central vision loss in patients. It is the most common eye disease affecting millions of people aged 50years or older, and is slowly becoming a major health problem worldwide. The disease mainly affects macula lutea, an oval-shaped pigmented area surrounding fovea near the center of retina, a region responsible for visual acuity. It is fairly a complex disease as genetics of patients, environmental triggers as well as risk factors such as age, family history of CVDs, diabetes, gender, obesity, race, hyperopia, iris color, smoking, diabetes, exposure to sun light and pyroptosis have all been clubbed together as probable causes of macular degeneration...
August 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28731031/nlrp9b-a-novel-rna-sensing-inflammasome-complex
#2
Chinh Ngo, Si Ming Man
Inflammasome sensors recognize pathogens and danger signals and assemble an immune signaling complex, which induces the secretion of pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis. A new study published in Nature now describes a new inflammasome sensor NLRP9b in intestinal epithelial cells, which in concert with the RNA sensor DHX9, recognize short dsRNA from Rotavirus.
July 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28726636/live-cell-visualization-of-gasdermin-d-driven-pyroptotic-cell-death
#3
Joseph K Rathkey, Bryan L Benson, Steven M Chirieleison, Jie Yang, Tsan S Xiao, George R Dubyak, Alex Y Huang, Derek W Abbott
Pyroptosis is a form of cell death important in defenses against pathogens, but which can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, gasdermin D (GSDMD), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has complicated our ability to understand the biology of this protein. Studies aimed at visualizing GSDMD have relied on expression of GSDMD fragments in epithelial cell lines that naturally lack GSDMD expression and also lack the proteases necessary to cleave GSDMD...
July 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28724943/aim2-inflammasome-mediated-pyroptosis-in-enterovirus-a71-infected-neuronal-cells-restricts-viral-replication
#4
Thinesshwary Yogarajah, Kien Chai Ong, David Perera, Kum Thong Wong
Encephalomyelitis is a well-known complication of hand, foot, and mouth disease (HFMD) due to Enterovirus 71 (EV71) infection. Viral RNA/antigens could be detected in the central nervous system (CNS) neurons in fatal encephalomyelitis but the mechanisms of neuronal cell death is not clearly understood. We investigated the role of absent in melanoma 2 (AIM2) inflammasome in neuronal cell death, and its relationship to viral replication. Our transcriptomic analysis, RT-qPCR, Western blot, immunofluorescence and flow cytometry studies consistently showed AIM2 gene up-regulation and protein expression in EV-A71-infected SK-N-SH cells...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28701426/dynamics-of-in-vivo-asc-speck-formation
#5
Paola Kuri, Nicole L Schieber, Thomas Thumberger, Joachim Wittbrodt, Yannick Schwab, Maria Leptin
Activated danger or pathogen sensors trigger assembly of the inflammasome adaptor ASC into specks, large signaling platforms considered hallmarks of inflammasome activation. Because a lack of in vivo tools has prevented the study of endogenous ASC dynamics, we generated a live ASC reporter through CRISPR/Cas9 tagging of the endogenous gene in zebrafish. We see strong ASC expression in the skin and other epithelia that act as barriers to insult. A toxic stimulus triggered speck formation and rapid pyroptosis in keratinocytes in vivo...
July 12, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28698859/inflammasome-as-a-therapeutic-target-for-cancer-prevention-and-treatment
#6
REVIEW
Huyen Trang Ha Thi, Suntaek Hong
Chronic inflammation is a critical modulator of carcinogenesis through secretion of inflammatory cytokines, which leads to the formation of an inflammatory microenvironment. In this process, the inflammasome plays an important role in the expression and activation of interleukin (IL)-1β and IL-18 to promote cancer development. The inflammasome is a multiprotein complex consisting of several nucleotide-binding domain and leucine-rich repeat containing receptor, adaptor proteins, and caspase 1 (CASP1). It senses the various intracellular (damage-associated molecular patterns) and extracellular (pathogen-associated molecular patterns) stimuli...
June 2017: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28695629/caspase-11-non-canonical-inflammasome-a-critical-sensor-of-intracellular-lps-in-macrophage-mediated-inflammatory-responses
#7
REVIEW
Young-Su Yi
Inflammatory responses mediated by macrophages are part of the innate immune system, whose role is to protect against invading pathogens. Lipopolysaccharide (LPS) found in the outer membrane of Gram-negative bacteria stimulate an inflammatory response by macrophages. During the inflammatory response, extracellular LPS are recognized by Toll-like receptor 4 (TLR4), one of the pattern recognition receptors (PRRs) that activates inflammatory signaling pathways and leads to the production of inflammatory mediators...
July 10, 2017: Immunology
https://www.readbyqxmd.com/read/28690332/caspases-control-antiviral-innate-immunity
#8
REVIEW
Huihui Chen, Xiaohan Ning, Zhengfan Jiang
Caspases are a family of cysteine proteases whose functions have been scrutinized intensively in recent years. Beyond their established roles in programmed cell death and inflammatory response, some caspases are also fundamental players in antiviral immunity by fine-tuning the levels of antiviral signaling adapters and cytokines, such as type I interferons, which serves as a major, sophisticated weapon against viruses. Viral infections can result in inflammasome activation and the initiation of cell death, including apoptosis and pyroptosis, and multiple caspases are significantly involved in these processes...
July 10, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28679757/enterovirus-71-inhibits-pyroptosis-through-cleavage-of-gsdmd
#9
Xiaobo Lei, Zhenzhen Zhang, Xia Xiao, Jianli Qi, Bin He, Jianwei Wang
Enterovirus 71 (EV71) can cause hand, foot, and mouth disease (HFMD) in young children. Severe infection with EV71 can lead to neurological complications and even death. However, the molecular basis of viral pathogenesis remain poorly understand. Here, we report that EV71 induces degradation of GSDMD, an essential component of pyroptosis. Remarkably, the viral protease 3C directly targets GSDMD and induces its cleavage, which is dependent on the protease activity. Further analyses show that the Q193-G194 pair within GSDMD is the cleavage site of 3C...
July 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28679753/on-the-death-rate-of-abortively-infected-cells-estimation-from-simian-human-immunodeficiency-virus-infection
#10
Ruian Ke, Mian-Er Cong, David Li, Gerardo Garcia-Lerma, Alan S Perelson
Progressive T cell depletion during chronic human immunodeficiency virus (HIV) infection is a key mechanism that leads to the development of AIDS. Recent studies have suggested that most T cells in the tissue die through pyroptosis triggered by abortive infection, i.e. infection of resting T cells where HIV failed to complete reverse transcription. However, the contribution of abortive infection to T cell loss and how quickly abortively infected cells die in vivo, key parameters for a quantitative understanding of T cell population dynamics, are not clear...
July 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28671960/stress-fibers-autophagy-and-necrosis-by-persistent-exposure-to-pm2-5-from-biomass-combustion
#11
Regina Dornhof, Christoph Maschowski, Anastasiya Osipova, Reto Gieré, Maximilian Seidl, Irmgard Merfort, Matjaz Humar
Fine particulate matter (PM2.5) can adversely affect human health. Emissions from residential energy sources have the largest impact on premature mortality globally, but their pathological and molecular implications on cellular physiology are still elusive. In the present study potential molecular consequences were investigated during long-term exposure of human bronchial epithelial BEAS-2B cells to PM2.5, collected from a biomass power plant. Initially, we observed that PM2.5 did not affect cellular survival or proliferation...
2017: PloS One
https://www.readbyqxmd.com/read/28660207/chlamydia-muridarum-infection-of-macrophages-stimulates-il-1%C3%AE-secretion-and-cell-death-via-activation-of-caspase-1-in-an-rip3-independent-manner
#12
Lixiang Chen, Xue Liu, Xin Yu, Rongrong Ren, Chao Wang, Rui Zhao, Guangxun Meng, Shun Li, Xiaohui Zhou
Chlamydiae are Gram-negative bacteria, which replicate exclusively in the infected host cells. Infection of the host cells by Chlamydiae stimulates the innate immune system leading to an inflammatory response, which is manifested not only by secretion of proinflammatory cytokines such as IL-1β from monocytes, macrophages, and dendritic cells, but also possibly by cell death mediated by Caspase-1 pyroptosis. RIP3 is a molecular switch that determines the development of necrosis or inflammation. However, the involvement of RIP3 in inflammasome activation by Chlamydia muridarum infection has not been clarified...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28654770/md-2-regulates-lps-induced-nlrp3-inflammasome-activation-and-il-1beta-secretion-by-a-myd88-nf-%C3%AE%C2%BAb-dependent-pathway-in-alveolar-macrophages-cell-line
#13
Man Luo, Lijuan Hu, Dandan Li, Yanying Wang, Yuting He, Lei Zhu, Weiying Ren
Myeloid differentiation protein 2 (MD-2) is required in the recognition of lipopolysaccharide (LPS) by toll-like receptor 4 (TLR4), and participates in LPS-induced alveolar macrophage (AM) inflammation during acute lung injury (ALI). Activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome aggravates inflammation in LPS-induced ALI. However, there is currently little known about the relationship between MD-2 signaling and the NLRP3 inflammasome. This study showed that NLRP3 expression, IL-1beta (IL-1β) secretion, and pyroptosis were up-regulated after LPS stimulation in the NR8383 AM cell-line...
June 24, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28652398/cutting-edge-eosinophils-undergo-caspase-1-mediated-pyroptosis-in-response-to-necrotic-liver-cells
#14
Daphne Palacios-Macapagal, Jane Connor, Tomas Mustelin, Thirumalai R Ramalingam, Thomas A Wynn, Todd S Davidson
Many chronic liver disorders are characterized by dysregulated immune responses and hepatocyte death. We used an in vivo model to study the immune response to necrotic liver injury and found that necrotic liver cells induced eosinophil recruitment. Necrotic liver induced eosinophil IL-1β and IL-18 secretion, degranulation, and cell death. Caspase-1 inhibitors blocked all of these responses. Caspase-1-mediated cell death with accompanying cytokine release is the hallmark of a novel form of cell death termed pyroptosis...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28647049/targeting-of-regulated-necrosis-in-kidney-disease
#15
Diego Martin-Sanchez, Jonay Poveda, Miguel Fontecha-Barriuso, Olga Ruiz-Andres, María Dolores Sanchez-Niño, Marta Ruiz-Ortega, Alberto Ortiz, Ana Belén Sanz
The term acute tubular necrosis was thought to represent a misnomer derived from morphological studies of human necropsies and necrosis was thought to represent an unregulated passive form of cell death which was not amenable to therapeutic manipulation. Recent advances have improved our understanding of cell death in acute kidney injury. First, apoptosis results in cell loss, but does not trigger an inflammatory response. However, clumsy attempts at interfering with apoptosis (e.g. certain caspase inhibitors) may trigger necrosis and, thus, inflammation-mediated kidney injury...
June 21, 2017: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/28636595/nlrp9b-inflammasome-restricts-rotavirus-infection-in-intestinal-epithelial-cells
#16
Shu Zhu, Siyuan Ding, Penghua Wang, Zheng Wei, Wen Pan, Noah W Palm, Yi Yang, Hua Yu, Hua-Bing Li, Geng Wang, Xuqiu Lei, Marcel R de Zoete, Jun Zhao, Yunjiang Zheng, Haiwei Chen, Yujiao Zhao, Kellie A Jurado, Ningguo Feng, Liang Shan, Yuval Kluger, Jun Lu, Clara Abraham, Erol Fikrig, Harry B Greenberg, Richard A Flavell
Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown...
June 29, 2017: Nature
https://www.readbyqxmd.com/read/28630490/pyroptosis-superinfection-and-the-maintenance-of-the-latent-reservoir-in-hiv-1-infection
#17
Dominik Wodarz, David N Levy
A long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments, we suggest that the death of latently infected cells brought about by pyroptosis, or to a lesser extent by superinfection, might be key mechanisms to account for the size and composition of the latent reservoir. Pyroptosis is a form of cell death that occurs in a resting (and thus latently infected) T cell when a productively infected cell attempts cell-to-cell transmission of virus...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625689/multiple-and-complex-influences-of-connexins-and-pannexins-on-cell-death
#18
REVIEW
Jérôme Gilleron, Diane Carette, Dominique Segretain, Georges Pointis
Cell death is a fundamental process for organogenesis, immunity and cell renewal. During the last decades a broad range of molecular tools were identified as important players for several different cell death pathways (apoptosis, pyroptosis, necrosis, autosis…). Aside from these direct regulators of cell death programs, several lines of evidence proposed connexins and pannexins as potent effectors of cell death. In the present review we discussed the potential roles played by connexins, pannexins and innexins in the different cell death programs at different scales from gap junction intercellular communication to protein-protein interactions...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28619472/gasdermins-effectors-of-pyroptosis
#19
REVIEW
Stephen B Kovacs, Edward A Miao
Pyroptosis is a form of lytic programmed cell death initiated by inflammasomes, which detect cytosolic contamination or perturbation. This drives activation of caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming domain (PFD) from the C-terminal repressor domain (RD). The PFD oligomerizes to form large pores in the membrane that drive swelling and membrane rupture. Gasdermin D is one of six (in humans) gasdermin family members; several other gasdermins have also been shown to form pores that cause pyroptosis after cleavage to activate their PFDs...
June 12, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28606793/mir-20b-inhibits-mycobacterium-tuberculosis-induced-inflammation-in-the-lung-of-mice-through-targeting-nlrp3
#20
Jun Lou, Yongli Wang, Zhimin Zhang, Weiqiang Qiu
Tuberculosis (TB) is one of immune-related disorders. Although dysregulation of miRNAs has been implicated in innate and adaptive immune response, the specific effect of miR-20b on TB has not been documented. In this study, downregulation of miR-20b and upregulation of NLRP3 were observed in macrophages of TB patients, increased levels of inflammatory factors secretion were observed in serum of TB patients. Next, we established a TB mice model by using M. tuberculosis infection and intravenous injection of miR-20b mimic...
June 9, 2017: Experimental Cell Research
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