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https://www.readbyqxmd.com/read/28432285/nod1-modulates-il-10-signalling-in-human-dendritic-cells
#1
Theresa Neuper, Kornelia Ellwanger, Harald Schwarz, Thomas A Kufer, Albert Duschl, Jutta Horejs-Hoeck
NOD1 belongs to the family of NOD-like receptors, which is a group of well-characterised, cytosolic pattern-recognition receptors. The best-studied function of NOD-like receptors is their role in generating immediate pro-inflammatory and antimicrobial responses by detecting specific bacterial peptidoglycans or by responding to cellular stress and danger-associated molecules. The present study describes a regulatory, peptidoglycan-independent function of NOD1 in anti-inflammatory immune responses. We report that, in human dendritic cells, NOD1 balances IL-10-induced STAT1 and STAT3 activation by a SOCS2-dependent mechanism, thereby suppressing the tolerogenic dendritic cell phenotype...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432149/cd73-on-t-cells-orchestrates-cardiac-wound-healing-after-myocardial-infarction-by-purinergic-metabolic-reprogramming
#2
Nadine Borg, Christina Alter, Nicole Görldt, Christoph Jacoby, Zhaoping Ding, Bodo Steckel, Christine Quast, Florian Bönner, Daniela Friebe, Sebastian Temme, Ulrich Flögel, Jürgen Schrader
Background -T-cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The pro-inflammatory "danger signal" adenosine triphosphate (ATP), released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T-cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action. Methods -Myocardial ischemia (50 min /reperfusion) was induced in global CD73(-/-) and CD4-CD73(-/-) mice...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28422993/th17-micro-milieu-regulates-nlrp1-dependent-caspase-5-activity-in-skin-autoinflammation
#3
Stephanie Zwicker, Eva Hattinger, Daniela Bureik, Aleksandra Batycka-Baran, Andreas Schmidt, Peter-Arne Gerber, Simon Rothenfusser, Michel Gilliet, Thomas Ruzicka, Ronald Wolf
IL-1β is a potent player in cutaneous inflammation and central for the development of a Th17 micro-milieu in autoinflammatory diseases including psoriasis. Its production is controlled at the transcriptional level and by subsequent posttranslational processing via inflammatory caspases. In this study, we detected inflammatory caspase-5 active in epidermal keratinocytes and in psoriatic skin lesions. Further, interferon-γ and interleukin-17A synergistically induced caspase-5 expression in cultured keratinocytes, which was dependent on the antimicrobial peptide psoriasin (S100A7)...
2017: PloS One
https://www.readbyqxmd.com/read/28420175/a-new-input-device-for-spastics-based-on-strain-gauge
#4
Niels Buchhold, Christian Baumgartner
This article presents a new sensor for use by people with spastic disorders and similar conditions and enables them to steer and control medical devices such as electric powered wheelchairs. As spastic patients often suffer from cramping of their extremities, which can then no longer be controlled, using a standard joystick while operating a powered wheelchair can lead to dangerous situations. To prevent this, we designed a sensor based on strain gauges, which is shaped like a flat disc that can be operated using any body part...
April 17, 2017: Sensors
https://www.readbyqxmd.com/read/28418387/mitochondria-are-the-powerhouses-of-immunity
#5
REVIEW
Evanna L Mills, Beth Kelly, Luke A J O'Neill
Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells...
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28417012/coordinating-antigen-cytosolic-delivery-and-danger-signaling-to-program-potent-cross-priming-by-micelle-based-nanovaccine
#6
Zhida Liu, Chang Zhou, Yan Qin, Zihao Wang, Luyao Wang, Xiuli Wei, Yinjian Zhou, Qicheng Li, Hang Zhou, Wenjun Wang, Yang-Xin Fu, Mingzhao Zhu, Wei Liang
Although re-activating cytotoxic T-cell (CTLs) response inside tumor tissues by checkpoint blockade has demonstrated great success in tumor immunotherapy, active induction of efficient endogenous CTL response by therapeutic vaccines has been largely hampered by inefficient cytosolic delivery of antigens and coordinated activation of dendritic cells (DCs) in lymph nodes. Here we show that polyethylene glycol-phosphatidylethanolamine (PEG-PE) micelles transform soluble peptides into α-helix to enable their efficient cytosolic delivery...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28416116/activation-of-a-plant-nlr-complex-through-heteromeric-association-with-an-autoimmune-risk-variant-of-another-nlr
#7
Diep T N Tran, Eui-Hwan Chung, Anette Habring-Müller, Monika Demar, Rebecca Schwab, Jeffery L Dangl, Detlef Weigel, Eunyoung Chae
When independently evolved immune receptor variants meet in hybrid plants, they can activate immune signaling in the absence of non-self recognition. Such autoimmune risk alleles have recurrently evolved at the DANGEROUS MIX2 (DM2) nucleotide-binding domain and leucine-rich repeat (NLR)-encoding locus in A. thaliana. One of these activates signaling in the presence of a particular variant encoded at another NLR locus, DM1. We show that the risk variants of DM1 and DM2d NLRs signal through the same pathway that is activated when plant NLRs recognize non-self elicitors...
April 11, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28410301/dendritic-cell-strategies-for-eliciting-mutation-derived-tumor-antigen-responses-in-patients
#8
Sreekumar Balan, John Finnigan, Nina Bhardwaj
Dendritic cells (DCs) are equipped for sensing danger signals and capturing, processing, and presenting antigens to naive or effector cells and are critical in inducing humoral and adaptive immunity. Successful vaccinations are those that activate DCs to elicit both cellular and humoral responses, as well as long-lasting memory response against the target of interest. Recently, it has become apparent that tumor cells can provide new sources of antigens through nonsynonymous mutations or frame-shift mutations, leading to potentially hundreds of mutation-derived tumor antigens (MTAs) or neoantigens...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410150/platelet-toll-like-receptors-in-thromboinflammation
#9
Lina Paola D' Atri, Mirta Schattner
Besides their undiscussed role in hemostasis and thrombosis, platelets are also key effector cells capable of assisting and modulating inflammatory reactions and immune responses. Platelets play a sentinel role in immune surveillance by recognizing danger signals from pathogens and cell damage through the expression of toll-like receptors (TLRs) on its surface and internal compartments. Platelets express all 10 TLRs transcripts and its signalosome, including adaptor proteins and transcription factors. The activation of these receptors in platelets triggers hemostatic and inflammatory responses which participate in the host's response to bacterial and viral infections, linking thrombosis with infection and immunity...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28406675/how-does-it-feel-a-signal-detection-approach-to-feeling-generation
#10
Anat Karmon-Presser, Gal Sheppes, Nachshon Meiran
Feeling, or the subjective emotional experience, is a fundamental element of the emotional reaction, yet past attempts to understand the mechanisms of feeling generation remain limited. The current study presents a signal detection theory (SDT) conceptualization of feeling generation. Accordingly, feeling, like other sensations, reflects an outcome of an inner decision regarding the emotional evidence, and, therefore, can be evaluated via 2 processes: evidence differentiation (d')-the ability to emotionally differentiate between external stimuli, given the essentially noisy evidence-and criterion (c)-the report threshold, or amount of evidence needed to have an intense reportable feeling...
April 13, 2017: Emotion
https://www.readbyqxmd.com/read/28405594/screening-for-novel-endogenous-inflammatory-stimuli-using-the-secreted-embryonic-alkaline-phosphatase-nf-%C3%AE%C2%BAb-reporter-assay
#11
Lorena Zuliani-Alvarez, Anna M Piccinini, Kim S Midwood
An immune response can be activated by pathogenic stimuli, as well as endogenous danger signals, triggering the activation of pattern recognition receptors and initiating signalling cascades that lead to inflammation. This method uses THP1-Blue™ cells, a human monocytic cell line which contains an embryonic alkaline phosphatase reporter gene allowing the detection of NF-κB-induced transcriptional activation. We validated this protocol by assessing NF-κB activation after stimulation of toll-like receptor 4 (TLR4) by two different agonists: lipopolysaccharide (LPS), derived from the cell wall of Gram negative bacteria, and tenascin-C, an extracellular matrix protein whose expression is induced upon tissue injury...
April 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28404637/surfactant-inhibits-atp-induced-release-of-interleukin-1%C3%AE-via-nicotinic-acetylcholine-receptors
#12
Soeren Backhaus, Anna Zakrzewicz, Katrin Richter, Jelena Damm, Sigrid Wilker, Gabriele Fuchs-Moll, Mira Kuellmar, Andreas Hecker, Ivan Manzini, Clemens Ruppert, J Michael McIntosh, Winfried Padberg, Veronika Grau
Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine of innate immunity involved in host defense. High systemic IL-1β; levels, however, cause life-threatening inflammatory diseases including systemic inflammatory response syndrome. In response to various danger signals, pro-IL-1β; is synthesized and stays in the cytoplasm unless a second signal such as extracellular ATP activates the inflammasome, which enables processing and release of mature IL-1β. As pulmonary surfactant is known for its anti-inflammatory properties, we hypothesize that surfactant inhibits ATP-induced release of IL-1β...
April 12, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28399013/caspase-recruitment-domain-9-microbiota-and-tryptophan-metabolism-dangerous-liaisons-in-inflammatory-bowel-diseases
#13
Bruno Lamas, Mathias L Richard, Harry Sokol
PURPOSE OF REVIEW: Inflammatory bowel diseases (IBDs) develop as a result of a combination of genetic predisposition, dysbiosis of the gut microbiota, and environmental influences. Here, we describe an example of how caspase recruitment domain 9 (CARD9), one of the numerous IBD susceptibility genes, participate to colitis susceptibility by shaping gut microbiota to produce tryptophan metabolites. RECENT FINDINGS: Recent study showed that CARD9 mice are more susceptible to colitis as a result of impaired interleukin 22 signaling pathway...
April 8, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28396716/tumor-reactive-stroma-in-cholangiocarcinoma-the-fuel-behind-cancer-aggressiveness
#14
EDITORIAL
Simone Brivio, Massimiliano Cadamuro, Mario Strazzabosco, Luca Fabris
Cholangiocarcinoma (CCA) is a highly aggressive epithelial malignancy still carrying a dismal prognosis, owing to early lymph node metastatic dissemination and striking resistance to conventional chemotherapy. Although mechanisms underpinning CCA progression are still a conundrum, it is now increasingly recognized that the desmoplastic microenvironment developing in conjunction with biliary carcinogenesis, recently renamed tumor reactive stroma (TRS), behaves as a paramount tumor-promoting driver. Indeed, once being recruited, activated and dangerously co-opted by neoplastic cells, the cellular components of the TRS (myofibroblasts, macrophages, endothelial cells and mesenchymal stem cells) continuously rekindle malignancy by secreting a huge variety of soluble factors (cyto/chemokines, growth factors, morphogens and proteinases)...
March 28, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28389651/unique-residues-in-the-atp-gated-human-p2x7-receptor-define-a-novel-allosteric-binding-pocket-for-the-selective-antagonist-az10606120
#15
Rebecca C Allsopp, Sudad Dayl, Ralf Schmid, Richard J Evans
The P2X7 receptor (P2X7R) for ATP is a therapeutic target for pathophysiological states including inflammation, pain management and epilepsy. This is facilitated by the predicted low side effect profile as the high concentrations of ATP required to activate the receptor are usually only found following cell damage/disease and so P2X7Rs respond to a "danger" signal and are not normally active. AZ10606120 is a selective antagonist for P2X7Rs (IC50 of ~10 nM) and ineffective at the P2X1R (at 10 μM). To determine the molecular basis of selectivity we generated a series of P2X7/1R chimeras and mutants...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28380377/farnesoid-x-receptor-regulation-of-the-nlrp3-inflammasome-underlies-cholestasis-associated-sepsis
#16
Haiping Hao, Lijuan Cao, Changtao Jiang, Yuan Che, Songyang Zhang, Shogo Takahashi, Guangji Wang, Frank J Gonzalez
Cholestasis is a common complication of sepsis, and the increased plasma levels of bile acids are predictive of sepsis-associated mortality. However, the exact mechanism by which cholestasis aggravates sepsis development remains elusive. Here, we show that bile acids are danger-associated molecular patterns (DAMPs) that can activate both signal 1 and 2 of the NLRP3 inflammasome in inflammatory macrophages. Mechanistically, bile acids induce a prolonged calcium influx and activate the NLRP3 inflammasome synergistically with ATP...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28380264/hsp70-potentiates-interferon-alpha-production-by-plasmacytoid-dendritic-cells-relevance-for-cutaneous-lupus-and-vitiligo-pathogenesis
#17
C Jacquemin, J Rambert, S Guillet, D Thiolat, N Boukhedouni, M-S Doutre, A-S Darrigade, K Ezzedine, P Blanco, A Taieb, K Boniface, J Seneschal
BACKGROUND: Plasmacytoid dendritic cells (pDC) are a subset of DC specialized in the production of type I interferon (IFN-α/β) and involved in various cutaneous inflammatory and autoimmune disorders, such as cutaneous lupus (CLE) and vitiligo. Heat-Shock proteins (HSP) are molecular chaperones essential for maintaining cellular functions, but can act as a danger signal during inflammation. OBJECTIVES: To decipher the role of HSP70 in the production of IFNα by pDC in CLE and vitiligo...
April 5, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28377744/non-neuronal-cells-in-the-hypothalamic-adaptation-to-metabolic-signals
#18
REVIEW
Alejandra Freire-Regatillo, Pilar Argente-Arizón, Jesús Argente, Luis Miguel García-Segura, Julie A Chowen
Although the brain is composed of numerous cell types, neurons have received the vast majority of attention in the attempt to understand how this organ functions. Neurons are indeed fundamental but, in order for them to function correctly, they rely on the surrounding "non-neuronal" cells. These different cell types, which include glia, epithelial cells, pericytes, and endothelia, supply essential substances to neurons, in addition to protecting them from dangerous substances and situations. Moreover, it is now clear that non-neuronal cells can also actively participate in determining neuronal signaling outcomes...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28377486/p2x7-deficiency-blocks-lesional-inflammasome-activity-and-ameliorates-atherosclerosis-in-mice
#19
Peter Stachon, Adrian Heidenreich, Julian Merz, Ingo Hilgendorf, Dennis Wolf, Florian Willecke, Sunaina von Garlen, Philipp Albrecht, Carmen Härdtner, Nicolas Ehrat, Natalie Hoppe, Jochen Reinöhl, Constantin von Zur Mühlen, Christoph Bode, Marco Idzko, Andreas Zirlik
Background -Extracellular ATP binds as a danger signal to purinergic receptor P2X7, promotes inflammasome assembly, and IL-1β expression. We hypothesized a functional role of the signal axis ATP - P2X7 in inflammasome activation and the chronic inflammation driving atherosclerosis. Methods -P2X7-competent and -deficient macrophages were isolated and stimulated with LPS, ATP, or both. To assess whether P2X7 may have a role in atherosclerosis, P2X7 expression was analyzed in aortic arches from LDLR(-/-) mice consuming high cholesterol diet (HCD) or chow diet...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28365315/response-inhibition-or-evaluation-of-danger-an-event-related-potential-study-regarding-the-origin-of-the-motor-interference-effect-from-dangerous-objects
#20
Peng Liu, Rong Cao, Xuhai Chen, Yonghui Wang
Previous studies have identified an interference effect from dangerous objects on prepared responses. However, its origin remains arguable. This study investigated the neural processes of this motor interference effect. The design adopted a motor priming paradigm mixed with a Go/NoGo task. Pictures of a left or right hand were used as primes, and green (Go signal) or red (NoGo signal) circles superimposed on dangerous or safe objects were used as targets. Participants were instructed to prepare the corresponding key press using the hand that was consistent with the handedness of the prime and not to execute until a Go signal appeared...
March 29, 2017: Brain Research
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