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https://www.readbyqxmd.com/read/28215228/hmgb1-protein-a-therapeutic-target-inside-and-outside-the-cell
#1
I Ugrinova, E Pasheva
High-mobility group box 1 protein (HMGB1) is a nonhistone chromosomal protein discovered more than 30 years ago. It is an abundant nuclear protein that has a dual function-in the nucleus, it binds DNA and participates in practically all DNA-dependent processes serving as an architectural factor. Outside the cell, HMGB1 plays a different role-it acts as an alarmine that activates a large number of HMGB1-"competent" cells and mediates a broad range of physiological and pathological responses. This universality makes it an attractive target for innovative therapeutic strategies in the treatment of various diseases...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28198366/th17-cells-express-st2-and-are-controlled-by-the-alarmin-il-33-in-the-small-intestine
#2
A Pascual-Reguant, J Bayat Sarmadi, C Baumann, R Noster, D Cirera-Salinas, C Curato, P Pelczar, S Huber, C E Zielinski, M Löhning, A E Hauser, E Esplugues
TH17 cells are major drivers of inflammation and involved in several autoimmune diseases. Tissue inflammation is a beneficial host response to infection, but it can also contribute to autoimmunity. The crosstalk between a tissue and the immune system during an inflammatory response is key for preserving tissue integrity and restoring physiological processes. However, how the inflamed tissue regulates the magnitude of an immune response by controlling pro-inflammatory T cells is not well characterized so far...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28192534/sm-p80-based-schistosomiasis-vaccine-mediated-epistatic-interactions-identified-potential-immune-signatures-for-vaccine-efficacy-in-mice-and-baboons
#3
Juan U Rojo, Michael W Melkus, Kameswara Rao Kottapalli, Oscar E Okiya, Justin Sudduth, Weidong Zhang, Adebayo J Molehin, Darrick Carter, Afzal A Siddiqui
Schistosomiasis is a neglected parasitic disease of major public health concern as it affects over 250 million people in developing countries. Currently there is no licensed vaccine available against schistosomiasis. The Schistosoma mansoni calpain protein, Sm-p80, is a leading vaccine candidate now ready to move to clinical trials. In order to better assess Sm-p80 vaccine immunogenicity; here we used a systems biology approach employing RNA-sequencing to identify gene signatures and epistatic interactions following Sm-p80 vaccination in mouse and baboon models that may predict vaccine efficacy...
2017: PloS One
https://www.readbyqxmd.com/read/28178282/trypanosoma-cruzi-high-mobility-group-b-tchmgb-can-act-as-an-inflammatory-mediator-on-mammalian-cells
#4
Pamela Cribb, Virginia Perdomo, Victoria L Alonso, Romina Manarin, Jorge Barrios-Payán, Brenda Marquina-Castillo, Luis Tavernelli, Rogelio Hernández-Pando
BACKGROUND: High Mobility Group B (HMGB) proteins are nuclear architectural factors involved in chromatin remodeling and important nuclear events. HMGBs also play key roles outside the cell acting as alarmins or Damage-associated Molecular Patterns (DAMPs). In response to a danger signal these proteins act as immune mediators in the extracellular milieu. Moreover, these molecules play a central role in the pathogenesis of many autoimmune and both infectious and sterile inflammatory chronic diseases...
February 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28176789/the-intraspecies-diversity-of-c-albicans-triggers-qualitatively-and-temporally-distinct-host-responses-that-determine-the-balance-between-commensalism-and-pathogenicity
#5
F A Schönherr, F Sparber, F R Kirchner, E Guiducci, K Trautwein-Weidner, A Gladiator, N Sertour, U Hetzel, G T T Le, N Pavelka, C d'Enfert, M-E Bougnoux, C F Corti, S LeibundGut-Landmann
The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28168040/role-of-the-il-33-st2-axis-in-sepsis
#6
REVIEW
Hui Xu, Heth R Turnquist, Rosemary Hoffman, Timothy R Billiar
Sepsis remains a major clinical problem with high morbidity and mortality. As new inflammatory mediators are characterized, it is important to understand their roles in sepsis. Interleukin 33 (IL-33) is a recently described member of the IL-1 family that is widely expressed in cells of barrier tissues. Upon tissue damage, IL-33 is released as an alarmin and activates various types of cells of both the innate and adaptive immune system through binding to the ST2/IL-1 receptor accessory protein complex. IL-33 has apparent pleiotropic functions in many disease models, with its actions strongly shaped by the local microenvironment...
2017: Military Medical Research
https://www.readbyqxmd.com/read/28167650/alarmins-feel-the-stress
#7
REVIEW
Peleg Rider, Elena Voronov, Charles A Dinarello, Ron N Apte, Idan Cohen
Over the last decade, danger-associated molecular pattern molecules, or alarmins, have been recognized as signaling mediators of sterile inflammatory responses after trauma and injury. In contrast with the accepted passive release models suggested by the "danger hypothesis," it was recently shown that alarmins can also directly sense and report damage by signaling to the environment when released from live cells undergoing physiological stress, even without loss of subcellular compartmentalization. In this article, we review the involvement of alarmins such as IL-1α, IL-33, IL-16, and high-mobility group box 1 in cellular and physiological stress, and suggest a novel activity of these molecules as central initiators of sterile inflammation in response to nonlethal stress, a function we denote "stressorins...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28147281/the-atypical-ubiquitin-e2-conjugase-ube2l3-is-an-indirect-caspase-1-target-and-controls-il-1%C3%AE-secretion-by-inflammasomes
#8
Matthew J G Eldridge, Julia Sanchez-Garrido, Gil Ferreira Hoben, Philippa J Goddard, Avinash R Shenoy
Caspase-1 activation by inflammasome signaling scaffolds initiates inflammation and antimicrobial responses. Caspase-1 proteolytically converts newly induced pro-interleukin 1 beta (IL-1β) into its mature form and directs its secretion, triggering pyroptosis and release of non-substrate alarmins such as interleukin 1 alpha (IL-1α) and HMGB1. While some caspase-1 substrates involved in these events are known, the identities and roles of non-proteolytic targets remain unknown. Here, we use unbiased proteomics to show that the UBE2L3 ubiquitin conjugase is an indirect target of caspase-1...
January 31, 2017: Cell Reports
https://www.readbyqxmd.com/read/28130045/hematopoietic-processes-in-eosinophilic-asthma
#9
Brittany M Salter, Roma Sehmi
Airway eosinophilia is a hallmark of allergic asthma and understanding mechanisms that promote increases in lung eosinophil numbers is important for effective pharmaco-therapeutic development. It has become evident that expansion of hemopoietic compartments in the bone marrow promotes differentiation and trafficking of mature eosinophils to the airways. Hematopoietic progenitor cells egress the bone marrow and home to the lungs, where in-situ differentiative processes within the tissue provide an ongoing source of pro-inflammatory cells...
January 24, 2017: Chest
https://www.readbyqxmd.com/read/28128358/galectin-3-released-in-response-to-traumatic-brain-injury-acts-as-an-alarmin-orchestrating-brain-immune-response-and-promoting-neurodegeneration
#10
Ping Kei Yip, Alejandro Carrillo-Jimenez, Paul King, Anna Vilalta, Koji Nomura, Chi Cheng Chau, Alexander Michael Scott Egerton, Zhuo-Hao Liu, Ashray Jayaram Shetty, Jordi L Tremoleda, Meirion Davies, Tomas Deierborg, John V Priestley, Guy Charles Brown, Adina Teodora Michael-Titus, Jose Luis Venero, Miguel Angel Burguillos
Traumatic brain injury (TBI) is currently a major cause of morbidity and poor quality of life in Western society, with an estimate of 2.5 million people affected per year in Europe, indicating the need for advances in TBI treatment. Within the first 24 h after TBI, several inflammatory response factors become upregulated, including the lectin galectin-3. In this study, using a controlled cortical impact (CCI) model of head injury, we show a large increase in the expression of galectin-3 in microglia and also an increase in the released form of galectin-3 in the cerebrospinal fluid (CSF) 24 h after head injury...
January 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28127491/sterile-neuroinflammation-and-strategies-for-therapeutic-intervention
#11
REVIEW
Manoj Banjara, Chaitali Ghosh
Sterile neuroinflammation is essential for the proper brain development and tissue repair. However, uncontrolled neuroinflammation plays a major role in the pathogenesis of various disease processes. The endogenous intracellular molecules so called damage-associated molecular patterns or alarmins or damage signals that are released by activated or necrotic cells are thought to play a crucial role in initiating an immune response. Sterile inflammatory response that occurs in Alzheimer's disease (AD), Parkinson's disease (PD), stroke, hemorrhage, epilepsy, or traumatic brain injury (TBI) creates a vicious cycle of unrestrained inflammation, driving progressive neurodegeneration...
2017: International Journal of Inflammation
https://www.readbyqxmd.com/read/28120021/matrix-metalloproteinase-14-triggers-an-anti-inflammatory-proteolytic-cascade-in-endotoxemia
#12
Alina Aguirre, Jorge Blázquez-Prieto, Laura Amado-Rodriguez, Inés López-Alonso, Estefanía Batalla-Solís, Adrián González-López, Moisés Sánchez-Pérez, Carlos Mayoral-Garcia, Ana Gutiérrez-Fernández, Guillermo M Albaiceta
: ᅟ: Matrix metalloproteinases can modulate the inflammatory response through processing of cyto- and chemokines. Among them, MMP-14 is a non-dispensable collagenase responsible for the activation of other enzymes, triggering a proteolytic cascade. To identify the role of MMP-14 during the pro-inflammatory response, wildtype and Mmp14 (-/-) mice were challenged with lipopolysaccharide. MMP-14 levels decreased after endotoxemia. Mutant animals showed 100% mortality, compared to 50% in wildtype mice...
January 24, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28115287/microbial-recognition-and-danger-signals-in-sepsis-and-trauma
#13
REVIEW
Steven L Raymond, David C Holden, Juan C Mira, Julie A Stortz, Tyler J Loftus, Alicia M Mohr, Lyle L Moldawer, Frederick A Moore, Shawn D Larson, Philip A Efron
Early host recognition of microbial invasion or damaged host tissues provides an effective warning system by which protective immune and inflammatory processes are initiated. Host tissues responsible for continuous sampling of their local environment employ cell surface and cytosolic pattern recognition receptors (PRRs) that provide redundant and overlapping identification of both microbial and host alarmins. Microbial products containing pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) serve as principle ligands for recognition by these PRRs...
January 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28063040/a-mouse-model-for-atopic-dermatitis-using-topical-application-of-vitamin-d3-or-of-its-analog-mc903
#14
Verena Moosbrugger-Martinz, Matthias Schmuth, Sandrine Dubrac
Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease with pruritus and high prevalence. Indeed, 15-30 % of children and 2-10 % of adults from industrialized countries are affected. Acute AD lesions are characterized by epidermal hyperplasia associated with a dominant Th2/Th17 immune response and dermal inflammatory infiltrates. Moreover, the expression of alarmins such as TSLP, IL-33, and IL-25 is upregulated in acute AD lesions. Topical application of vitamin D3 or of its low-calcemic analog MC903 induces changes in skin morphology and inflammation resembling immune perturbations observed in acute lesions of patients with AD...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28057209/mechanisms-of-chromatin-remodeling-and-repurposing-during-extracellular-translocation
#15
D S Pisetsky
Chromatin is a highly conserved molecular structure that provides genetic information to regulate cell function. Comprised of DNA, histones and interacting proteins, chromatin is inherently dynamic and subject to remodeling. While usually conceptualized as an intranuclear event, remodeling can also involve extracellular movement. Indeed, chromatin can translocate entirely from the inside to the outside of the cell during cell death processes that include apoptosis, necrosis, and NETosis. During these processes, DNA and proteins can undergo other changes impacting on their activity...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28053237/highly-selective-cleavage-of-cytokines-and-chemokines-by-the-human-mast-cell-chymase-and-neutrophil-cathepsin-g
#16
Zhirong Fu, Michael Thorpe, Rahel Alemayehu, Ananya Roy, Jukka Kervinen, Lawrence de Garavilla, Magnus Åbrink, Lars Hellman
Human mast cell chymase (HC) and human neutrophil cathepsin G (hCG) show relatively similar cleavage specificities: they both have chymotryptic activity but can also cleave efficiently after leucine. Their relatively broad specificity suggests that they may cleave almost any substrate if present in high enough concentrations or for a sufficiently long time. A number of potential substrates have been identified for these enzymes and, recently, these enzymes have also been implicated in regulating cytokine activity by cleaving numerous cytokines and chemokines...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27994953/tlr4-dependant-pro-inflammatory-effects-of-hmgb1-on-human-adipocyte
#17
Manoj Kumar Gunasekaran, Anne-Laurence Virama-Latchoumy, Anne-Claire Girard, Cynthia Planesse, Alexis Guérin-Dubourg, Lars Ottosson, Ulf Andersson, Maya Césari, Régis Roche, Laurence Hoareau
Chronic low grade inflammation is one of the major metabolic disorders in case of obesity and associated pathologies. By its important secretion function, the role of adipose tissue in this metabolic low grade inflammation is well known. Recently, it was demonstrated that the alarmin high mobility group box protein 1 (HMGB1) is involved in obesity-related pathologies by its increased serum levels in obese compared to normal weight individuals, and by its pro-inflammatory effects. However, the role of HMGB1 on adipocytes inflammation is poorly documented and we propose to investigate this point...
October 2016: Adipocyte
https://www.readbyqxmd.com/read/27993995/in-neonates-s100a8-s100a9-alarmins-prevent-the-expansion-of-a-specific-inflammatory-monocyte-population-promoting-septic-shock
#18
Anna S Heinemann, Sabine Pirr, Beate Fehlhaber, Lara Mellinger, Johanna Burgmann, Mandy Busse, Marco Ginzel, Judith Friesenhagen, Maren von Köckritz-Blickwede, Thomas Ulas, Constantin S von Kaisenberg, Johannes Roth, Thomas Vogl, Dorothee Viemann
The high susceptibility of newborn infants to sepsis is ascribed to an immaturity of the neonatal immune system, but the molecular mechanisms remain unclear. Newborn monocytes massively release the alarmins S100A8/S100A9. In adults, these are major regulators of immunosuppressive myeloid-derived suppressor cells (MDSCs). We investigated whether S100A8/S100A9 cause an expansion of monocytic MDSCs (Mo-MDSCs) in neonates, thereby contributing to an immunocompromised state. Mo-MDSCs have been assigned to CD14(+)/human leukocyte antigen (HLA)-DR(-)(/low)/CD33(+) monocytes in humans and to CD11b(+)/Gr-1(int)/Ly6G(-)/Ly6C(hi) cells in mice...
December 19, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27992569/interleukin-33-and-rank-l-interplay-in-the-alveolar-bone-loss-associated-to-periodontitis
#19
Olivier Lapérine, Alexandra Cloitre, Jocelyne Caillon, Olivier Huck, Isaac Maximiliano Bugueno, Paul Pilet, Sophie Sourice, Elodie Le Tilly, Gaby Palmer, Jean-Luc Davideau, Valérie Geoffroy, Jérôme Guicheux, Sarah Beck-Cormier, Philippe Lesclous
INTRODUCTION: Chronic Periodontitis (CP) is an inflammatory disease of bacterial origin that results in alveolar bone destruction. Porphyromonas gingivalis (Pg), one of the main periopathogens, initiates an inflammatory cascade by host immune cells thereby increasing recruitment and activity of osteoclasts, the bone resorbing cells, through enhanced production of the crucial osteoclastogenic factor, RANK-L. Antibodies directed against some cytokines (IL-1β, IL-6 and TNF-α) failed to exhibit convincing therapeutic effect in CP...
2016: PloS One
https://www.readbyqxmd.com/read/27918564/interleukin-33-induced-expression-of-pibf1-by-decidual-b-cells-protects-against-preterm-labor
#20
Bihui Huang, Azure N Faucette, Michael D Pawlitz, Bo Pei, Joshua W Goyert, Jordan Zheng Zhou, Nadim G El-Hage, Jie Deng, Jason Lin, Fayi Yao, Robert S Dewar, Japnam S Jassal, Maxwell L Sandberg, Jing Dai, Montserrat Cols, Cong Shen, Lisa A Polin, Ronald A Nichols, Theodore B Jones, Martin H Bluth, Karoline S Puder, Bernard Gonik, Nihar R Nayak, Elizabeth Puscheck, Wei-Zen Wei, Andrea Cerutti, Marco Colonna, Kang Chen
Preterm birth (PTB) is a leading cause of neonatal death worldwide. Intrauterine and systemic infection and inflammation cause 30-40% of spontaneous preterm labor (PTL), which precedes PTB. Although antibody production is a major immune defense mechanism against infection, and B cell dysfunction has been implicated in pregnancy complications associated with PTL, the functions of B cells in pregnancy are not well known. We found that choriodecidua of women undergoing spontaneous PTL harbored functionally altered B cell populations...
January 2017: Nature Medicine
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