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https://www.readbyqxmd.com/read/28636595/nlrp9b-inflammasome-restricts-rotavirus-infection-in-intestinal-epithelial-cells
#1
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 21, 2017: Nature
https://www.readbyqxmd.com/read/28630490/pyroptosis-superinfection-and-the-maintenance-of-the-latent-reservoir-in-hiv-1-infection
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28599978/25-hydroxycholesterol-induces-both-p2x7-dependent-pyroptosis-and-caspase-dependent-apoptosis-in-human-skin-model-new-insights-into-degenerative-pathways
#6
Elodie Olivier, Mélody Dutot, Anne Regazzetti, Olivier Laprevote, Patrice Rat
Degenerative diseases are characterized by both cell death and inflammation, which involve different pathways such as apoptosis and pyroptosis. Oxysterols, oxidized derivatives of cholesterol, are known to act as key actors in degenerative disorders such as skin photoaging. We hypothesize that oxysterols could be implicated in either apoptosis or pyroptosis, or both. The aim of our study was first to quantify oxysterol levels in keratinocytes as a function of aging and UV irradiation. Second, we evaluated the effects of 25-OH oxysterol on apoptosis and pyroptosis hallmarks in keratinocytes...
June 6, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28585198/fat-cell-and-fatty-acid-turnover-in-obesity
#7
Atilla Engin
The ratio of free fatty acid (FFA) turnover decreases significantly with the expansion of white adipose tissue. Adipose tissue and dietary saturated fatty acid levels significantly correlate with an increase in fat cell size and number. Inhibition of adipose triglyceride lipase leads to an accumulation of triglyceride, whereas inhibition of hormone-sensitive lipase leads to the accumulation of diacylglycerol. The G0/G1 switch gene 2 increases lipid content in adipocytes and promotes adipocyte hypertrophy through the restriction of triglyceride turnover...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28579961/characterization-of-annexin-v-fusion-with-the-superfolder-gfp-in-liposomes-binding-and-apoptosis-detection
#8
Abdul Qader Abbady, Aya Twair, Bouthaina Ali, Hossam Murad
Programed cell death is a critical and unavoidable part of life. One of the most widely used markers for dying cells, by apoptosis or pyroptosis, is the redistribution of phosphatidylserine (PS) from the inner to the outer plasma membrane leaflet. Annexin V protein is a sensitive and specific probe to mark this event because of its high affinity to the exposed PS. Beyond that, annexin V can bind to any PS-containing phospholipid bilayer of almost all tiny forms of membranous vesicles like blood platelets, exosomes, or even nanostructured liposomes...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28577894/proteolytic-control-of-regulated-necrosis
#9
REVIEW
Johaiber Fuchslocher Chico, Carina Saggau, Dieter Adam
Proteases control most of the physiological processes that occur in a cell. This particularly applies to apoptosis, the most well-studied form of cell death, where proteolysis by cysteine-aspartic proteases (caspases) is the primary mechanism for both initiation and execution of cell suicide. In contrast, the impact of proteolysis on other, non-apoptotic cell death pathways (summarized under the term "regulated necrosis", RN) has long been enigmatic, but has clearly been confirmed by a number of recent groundbreaking discoveries...
May 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28576828/the-intracellular-chloride-channel-proteins-clic1-and-clic4-induce-il-1%C3%AE-transcription-and-activate-the-nlrp3-inflammasome
#10
Raquel Domingo-Fernández, Rebecca C Coll, Jay Kearney, Samuel Breit, Luke Aj O'Neill
The NLRP3 inflammasome is a multiprotein complex that regulates the activation of caspase-1 leading to the maturation of the pro-inflammatory cytokines IL-1β and IL-18, and promoting pyroptosis. Classically, the NLRP3 inflammasome in murine macrophages is activated by the recognition of pathogen-associated molecular patterns and by many structurally unrelated factors. Understanding the precise mechanism of NLRP3 activation by such wide array of stimuli remains elusive, but several signaling events, including cytosolic efflux and influx of select ions have been suggested...
June 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28575874/mitochondrion-associated-protein-peroxiredoxin-3-promotes-benign-prostatic-hyperplasia-through-autophagy-suppression-and-pyroptosis-activation
#11
Min-Yao Jiang, Zhao-Dong Han, Wenjiao Li, Fei Yue, Jianheng Ye, Bowei Li, Zhiduan Cai, Jian-Ming Lu, Weimin Dong, Xianhan Jiang, Weide Zhong, Huichan He, Leyuan Liu
Benign prostatic hyperplasia (BPH) is one of the most common diseases in the senior men and age plays an important role in the initiation and development of BPH. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles such as mitochondria and suppress pyroptosis, a type of cell death that stimulates inflammatory responses and growth of other cells around. Peroxiredoxin 3 (PRDX3) is the only mitochondrion-associated member of peroxiredoxin family enzymes that exert their protective antioxidant role in cells through their peroxidase activity...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28570638/detection-of-a-microbial-metabolite-by-sting-regulates-inflammasome-activation-in-response-to-chlamydia-trachomatis-infection
#12
Steve J Webster, Sven Brode, Lou Ellis, Timothy J Fitzmaurice, Matthew J Elder, Nelson O Gekara, Panagiotis Tourlomousis, Clare Bryant, Simon Clare, Ronnie Chee, Hill J S Gaston, Jane C Goodall
The innate immune system is a critical component of host defence against microbial pathogens, but effective responses require an ability to distinguish between infectious and non-infectious insult to prevent inappropriate inflammation. Using the important obligate intracellular human pathogen Chlamydia trachomatis; an organism that causes significant immunopathology, we sought to determine critical host and pathogen factors that contribute to the induction of inflammasome activation. We assayed inflammasome activation by immunoblotting and ELISA to detect IL-1β processing and LDH release to determine pyroptosis...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28569730/inflammasomes-and-il-1-biology-in-the-pathogenesis-of-allograft-dysfunction
#13
REVIEW
S Samuel Weigt, Vyacheslav Palchevskiy, John A Belperio
Inflammasomes are high-molecular-weight cytosolic complexes that mediate the activation of caspases. There are many inflammasomes, and each is influenced by a unique pattern-recognition receptor response. Two signals are typically involved in the inflammasome pathways. Signal one involves recognition of pathogen-associated molecular patterns (PAMPs), such as LPS or other colonizing/invading microbes, that interact with TLRs, which induce the downstream production of pro-IL-1β. This is followed by signal two, which involves recognition of PAMPs or damage-associated molecular patterns (DAMPs), such as uric acid or ATP, via NLRP3, which leads to caspase-1-dependent cleavage of pro-IL-1β to active IL-1β and pyroptosis...
June 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28564720/inflammasomes-in-liver-fibrosis
#14
Fernando Alegre, Pablo Pelegrin, Ariel E Feldstein
Cell death and inflammation are two central elements in the development of liver fibrosis. Inflammasomes are intracellular multiprotein complexes expressed in both hepatocytes and nonparenchymal cells in the liver that are key regulators of inflammation and cell fate. They respond to cellular danger signals by activating caspase 1, releasing the proinflammatory cytokines IL-1β and IL-18, as well as initiating a novel pathway of programmed cell death termed "pyroptosis." These processes can initiate and perpetuate an abnormal wound-healing response with the principle cellular target being the activation of hepatic stellate cells...
May 2017: Seminars in Liver Disease
https://www.readbyqxmd.com/read/28551077/lipopolysaccharide-detection-across-the-kingdoms-of-life
#15
REVIEW
Jonathan C Kagan
Studies in recent years have uncovered a diverse set of eukaryotic receptors that recognize lipopolysaccharide (LPS), the major outer-membrane component of Gram-negative bacteria. Indeed, Toll-like receptors, G-protein-coupled receptors, integrins, receptor-like kinases, and caspases have emerged as important LPS-interacting proteins. In this review, the mammalian receptors that detect LPS are described. I highlight how no host protein is involved in all LPS responses, but a single lipid (phosphatidylinositol-4,5-bisphosphate) regulates many LPS responses, including endocytosis, phagocytosis, inflammation, and pyroptosis...
May 24, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28539262/synthetic-anti-endotoxin-peptides-inhibit-cytoplasmic-lps-mediated-responses
#16
Anja Pfalzgraff, Lena Heinbockel, Qi Su, Klaus Brandenburg, Günther Weindl
Toll-like receptor (TLR) 4-independent recognition of lipopolysaccharide (LPS) in the cytosol by inflammatory caspases leads to non-canonical inflammasome activation and induction of IL-1 secretion and pyroptosis. The discovery of this novel mechanism has potential implications for the development of effective drugs to treat sepsis since LPS-mediated hyperactivation of caspases is critically involved in endotoxic shock. Previously, we demonstrated that Pep19-2.5, a synthetic anti-endotoxin peptide, efficiently neutralises pathogenicity factors of Gram-negative and Gram-positive bacteria and protects against sepsis in vivo...
May 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28535504/long-non-coding-rna-kcnq1ot1-promotes-cataractogenesis-via-mir-214-and-activation-of-the-caspase-1-pathway
#17
Xin Jin, Hao Jin, Yan Shi, Yiyuan Guo, Hong Zhang
BACKGROUND/AIMS: KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain. Imprinted genes are positive regulators of apoptosis, one of the forms of cell death related to cataract formation, and thus may provide novel therapeutic targets for cataract treatment. Here, we studied the role of non-coding RNAs(ncRNA) in cataract formation. METHODS: Human lens epithelium cells (HLECs) were treated with H2O2, and the expression of KCNQ1OT1 and miR-214 was detected by qRT-PCR...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28533778/dnase1l3-regulates-inflammasome-dependent-cytokine-secretion
#18
Guilan Shi, Kennady N Abbott, Wenbo Wu, Russell D Salter, Peter A Keyel
Pediatric-onset systemic lupus erythematosus arises in humans and mice lacking the endonuclease Dnase1L3. When Dnase1L3 is absent, DNA from circulating apoptotic bodies is not cleared, leading to anti-DNA antibody production. Compared to early anti-DNA and anti-chromatin responses, other autoantibody responses and general immune activation in Dnase1L3(-/-) mice are greatly delayed. We investigated the possibility that immune activation, specifically inflammasome activation, is regulated by Dnase1L3. Here, we report that Dnase1L3 inhibition blocked both NLR family, pyrin domain containing 3 (NLRP3) and NLRC4 inflammasome-mediated release of high-mobility group box 1 protein and IL-1β...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#19
Sannula Kesavardhana, Thirumala-Devi Kanneganti
Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein - apoptosis associated speck-like protein containing a caspase-activation and -recruitment domain (ASC) - activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens...
May 20, 2017: International Immunology
https://www.readbyqxmd.com/read/28525771/return-of-the-ice-age-caspases-safeguard-against-inflammatory-cell-death
#20
Marcin Poreba, Guy Salvesen
In a recent issue of Cell Chemical Biology, Taabazuing et al. (2017) reveal a bidirectional interplay between pathways leading to apoptosis and pyroptosis, two forms of regulated cell death with opposing inflammatory outcomes. The outcome is sealed by differential cleavage of the key pyroptosis execution substrate gasdermin D such that inflammatory caspases activate it but apoptotic caspases prevent its activation.
May 18, 2017: Cell Chemical Biology
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