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Protease and inflammation

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https://www.readbyqxmd.com/read/28646094/immune-mediated-effects-targeting-hepatitis-c-virus-in-a-syngeneic-replicon-cell-transplantation-mouse-model
#1
Sepideh Levander, Fredrik Holmström, Lars Frelin, Gustaf Ahlén, Daniel Rupp, Gang Long, Ralf Bartenschlager, Matti Sällberg
OBJECTIVE: HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells. DESIGN: A total of 5 million H-2(b) positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2(b)-restricted mice...
June 23, 2017: Gut
https://www.readbyqxmd.com/read/28642633/proteases-revisited-roles-and-therapeutic-implications-in-fibrosis
#2
REVIEW
Jakub Kryczka, Joanna Boncela
Proteases target many substrates, triggering changes in distinct biological processes correlated with cell migration, EMT/EndMT and fibrosis. Extracellular protease activity, demonstrated by secreted and membrane-bound protease forms, leads to ECM degradation, activation of other proteases (i.e., proteolysis of nonactive zymogens), decomposition of cell-cell junctions, release of sequestered growth factors (TGF-β and VEGF), activation of signal proteins and receptors, degradation of inflammatory inhibitors or inflammation-related proteins, and changes in cell mechanosensing and motility...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28634018/distribution-subtype-population-and-ige-positivity-of-mast-cells-in-chronic-rhinosinusitis-with-nasal-polyps
#3
Shintaro Baba, Kenji Kondo, Maho Suzukawa, Ken Ohta, Tatsuya Yamasoba
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) has been categorized into 2 subtypes in the Asian population: eosinophilic chronic rhinosinusitis (ECRS; similar to CRSwNP in Western countries) and non-ECRS (characterized by inflammation dominated by T-helper cell type 1). The pathogenesis of CRSwNP and the role of mast cells are poorly understood. OBJECTIVE: To investigate the distribution, phenotypes, and immunoglobulin E (IgE) positivity of mast cells in these 2 subtypes of CRSwNP...
June 17, 2017: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28632925/a-kallikrein-targeting-rna-aptamer-inhibits-the-intrinsic-pathway-of-coagulation-and-reduces-bradykinin-release
#4
K-A Steen-Burrell, J Layzer, B A Sullenger
BACKGROUND: Plasma kallikrein is a serine protease that plays an integral role in many biological processes including coagulation, inflammation, and fibrinolysis. The main function of kallikrein in coagulation is the amplification of activated factor XIIa (FXIIa) generation which ultimately leads to thrombin generation and fibrin clot formation. Kallikrein is generated by FXIIa-mediated cleavage of the zymogen, prekallikrein which is usually complexed with the nonenzymatic cofactor, high-molecular-weight kininogen (HK)...
June 20, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28631213/the-constitutive-protease-release-by-primary-human-acute-myeloid-leukemia-cells
#5
Maria Honnemyr, Øystein Bruserud, Annette K Brenner
INTRODUCTION: Acute myeloid leukemia (AML) cells show constitutive release of matrix metalloproteases and their inhibitors. We now investigated this constitutive release of protease/protease regulators associated with carcinogenesis (ADAM12, uPA, cystatin B), angiogenesis (serpin E1, uPA, CD147), cancer cell migration (uPA, cystatin C), coagulation (ADAM TS13, serpin C1), inflammation (fetuin A, caspase 1, cystatin C), monocytic differentiation (CFD) or regulation of hematopoiesis (neutrophil elastase)...
June 19, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28630087/paucimannose-rich-n-glycosylation-of-spatiotemporally-regulated-human-neutrophil-elastase-modulates-its-immune-functions
#6
Ian Loke, Ole Østergaard, Niels H H Heegaard, Nicolle H Packer, Morten Thaysen-Andersen
Human neutrophil elastase (HNE) is an important N-glycosylated serine protease in the innate immune system, but the structure and immune-modulating functions of HNE N-glycosylation remain undescribed. Herein, LC-MS/MS-based glycan, glycopeptide and glycoprotein profiling were utilised to first determine the heterogeneous N-glycosylation of HNE purified from neutrophil lysates and then from isolated neutrophil granules of healthy individuals. The spatiotemporal expression of HNE during neutrophil activation and the biological importance of its N-glycosylation were also investigated using immunoblotting, cell surface capture, native MS, receptor interaction, protease inhibition, and bacteria growth assays...
June 19, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28615200/kallikrein-related-peptidase-5-contributes-to-h3n2-influenza-virus-infection-in-human-lungs
#7
Melia Magnen, Fabien Gueugnon, Antoine Guillon, Thomas Baranek, Virginie C Thibault, Agnès Petit-Courty, Simon J de Veer, Jonathan Harris, Alison A Humbles, Mustapha Si-Tahar, Yves Courty
The HA (hemagglutinin) of influenza virus must be activated by proteolysis before the virus can become infectious. Previous studies have indicated that HA cleavage is driven by membrane-bound or extracellular serine proteases in the respiratory tract. However, there is still uncertainty as to which proteases are critical for activating the HA of seasonal influenza A viruses (IAV) in humans. This study focuses on human KLK1 and KLK5, two of the 15 serine proteases known as the kallikrein-related peptidases (KLK)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28612481/review-biological-and-molecular-differences-between-tail-regeneration-and-limb-scarring-in-lizard-an-inspiring-model-addressing-limb-regeneration-in-amniotes
#8
REVIEW
Lorenzo Alibardi
Tissue regeneration in lizards represents a unique model of regeneration and scarring in amniotes. The tail and limb contain putative stem cells but also dedifferentiating cells contribute to regeneration. Following tail amputation, inflammation is low and cell proliferation high, leading to regeneration while the intense inflammation in the limb leads to low proliferation and scarring. FGFs stimulate tail and limb regeneration and are present in the wound epidermis and blastema while they disappear in the limb wound epidermis 2-3 weeks postamputation in the scarring outgrowth...
June 14, 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/28606938/peptide-mediated-mast-cell-activation-ligand-similarities-for-receptor-recognition-and-protease-induced-regulation
#9
REVIEW
Lei Lu, Marianna Kulka, Larry D Unsworth
MCs are crucial regulators of the innate immune response. MC degranulation is a rapid response mechanism that allows for the release of a stored plethora of inflammatory mediators, including histamine, heparin, various serine proteases, chemokines, and cytokines. The activation of MCs can lead to the de novo expression of a variety of chemokines and cytokines that can influence a variety of outcomes: inflammation, angiogenesis, and others. A variety of IgE-independent mediators, including IgG, cytokines, chemokines, exogenous molecules, drugs, and cationic peptides, and others, can directly trigger MC activation...
June 12, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28599247/inflammasomes-the-cardinal-pathology-mediators-are-activated-by-pathogens-allergens-and-mutagens-a-critical-review-with-focus-on-nlrp3
#10
REVIEW
Seema Patel
Inflammation is a pivotal defense system of body. Unfortunately, when homeostasis falters, the same inflammatory mechanism acts as a double-edged sword, and turns offensive, paving the path for a broad array of pathologies. A multi-protein complex termed as inflammasome perceives the PAMPs (pathogen associated molecular patterns) and DAMPs (danger associated molecular patterns), executing immune responses. This activation predominantly encompasses the elaboration of effector cytokines IL-1β, IL-18, and the cysteine proteases (caspase 1 and 11)...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28596972/targets-of-neutrophil-influx-and-weaponry-therapeutic-opportunities-for-chronic-obstructive-airway-disease
#11
REVIEW
Carina Kärrman Mårdh, James Root, Mohib Uddin, Kristina Stenvall, Anna Malmgren, Kostas Karabelas, Matthew Thomas
Neutrophils are important effector cells of antimicrobial immunity in an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), there is excessive infiltration and activation of neutrophils, subsequent production of reactive oxygen species, and release of serine proteases, matrix metalloproteinases, and myeloperoxidase-resulting in collateral damage as the cells infiltrate into the tissue...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28596294/the-metalloproteinase-adam8-promotes-leukocyte-recruitment-in-vitro-and-in-acute-lung-inflammation
#12
Daniela Dreymueller, Jessica Pruessmeyer, Julian Schumacher, Sandra Fellendorf, Franz Martin Hess, Anke Seifert, Aaron Babendreyer, Joerg Walter Bartsch, Andreas Ludwig
Alveolar leukocyte recruitment is a hallmark of acute lung inflammation and involves transmigration of leukocytes through endothelial and epithelial layers. The disintegrin and metalloproteinase (ADAM) 8 is expressed on human isolated leukocytic cells and can be further upregulated on cultured endothelial and epithelial cells by proinflammatory cytokines. By shRNA mediated knockdown we show that leukocytic ADAM8 is required on monocytic THP-1 cells for chemokine-induced chemotaxis as well as transendothelial and transepithelial migration...
June 8, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28594052/coagulation-factor-and-protease-pathways-in-thrombosis-and-cardiovascular-disease
#13
Hugo Ten Cate, Tilman M Hackeng, Pablo García de Frutos
The biochemical characterization of the proteolytic pathways that constitute blood coagulation was one of the most relevant achievements in biomedical research during the second half of the 20th century. Understanding these pathways was of crucial importance for improving global health through application in haemostasis and thrombosis pathologies. Immediately after the cloning of the genes corresponding to these proteins, mutations were discovered in them that were associated with imbalances in haemostasis...
June 8, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28591228/a-secondary-wave-of-neutrophil-infiltration-causes-necrosis-and-ulceration-in-lesions-of-experimental-american-cutaneous-leishmaniasis
#14
Alex G Peniche, Diana L Bonilla, Gloria I Palma, Peter C Melby, Bruno L Travi, E Yaneth Osorio
We evaluated the importance of neutrophils in the development of chronic lesions caused by L. Viannia spp. using the hamster as experimental model of American Cutaneous Leishmaniasis (ACL). Neutrophils infiltrated the lesion within the first six hours post-infection. Inhibition of this early infiltration using a polyclonal antibody or cyclophosphamide was associated with transient parasite control but the protective effect vanished when lesions became clinically apparent. At lesion onset (approximately 10 days p...
2017: PloS One
https://www.readbyqxmd.com/read/28589099/serine-protease-inhibitors-in-ticks-an-overview-of-their-role-in-tick-biology-and-tick-borne-pathogen-transmission
#15
REVIEW
Adrien A Blisnick, Thierry Foulon, Sarah I Bonnet
New tick and tick-borne pathogen control approaches that are both environmentally sustainable and which provide broad protection are urgently needed. Their development, however, will rely on a greater understanding of tick biology, tick-pathogen, and tick-host interactions. The recent advances in new generation technologies to study genomes, transcriptomes, and proteomes has resulted in a plethora of tick biomacromolecular studies. Among these, many enzyme inhibitors have been described, notably serine protease inhibitors (SPIs), whose importance in various tick biological processes is only just beginning to be fully appreciated...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28589098/manipulation-of-neutrophils-by-porphyromonas-gingivalis-in-the-development-of-periodontitis
#16
REVIEW
Maja Sochalska, Jan Potempa
The pathogenesis of the chronic periodontal disease is associated with a skewed host inflammatory response to periodontal pathogens, such as Porphyromonas gingivalis, that accounts for the majority of periodontal tissue damage. Neutrophils are the most abundant leukocytes in periodontal pockets and depending on the stage of the disease, also plentiful PMNs are present in the inflamed gingival tissue and the gingival crevice. They are the most efficient phagocytes and eliminate pathogens by a variety of means, which are either oxygen-dependent or -independent...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28587383/mechanism-of-the-protective-effects-of-the-combined-treatment-with-rhynchophylla-total-alkaloids-and-sinapine-thiocyanate-against-a-prothrombotic-state-caused-by-vascular-endothelial-cell-inflammatory-damage
#17
Yunlun Li, Xinya Zhang, Wenqing Yang, Chao Li, Yanjun Chu, Haiqiang Jiang, Zhenzhen Shen
The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28569748/the-critical-role-of-senp1-mediated-gata2-desumoylation-in-promoting-endothelial-activation-in-graft-arteriosclerosis
#18
Cong Qiu, Yuewen Wang, Haige Zhao, Lingfeng Qin, Yanna Shi, Xiaolong Zhu, Lin Song, Xiaofei Zhou, Jian Chen, Hong Zhou, Haifeng Zhang, George Tellides, Wang Min, Luyang Yu
Data from clinical research and our previous study have suggested the potential involvement of SENP1, the major protease of post-translational SUMOylation, in cardiovascular disorders. Here, we investigate the role of SENP1-mediated SUMOylation in graft arteriosclerosis (GA), the major cause of allograft failure. We observe an endothelial-specific induction of SENP1 and GATA2 in clinical graft rejection specimens that show endothelial activation-mediated vascular remodelling. In mouse aorta transplantation GA models, endothelial-specific SENP1 knockout grafts demonstrate limited neointima formation with attenuated leukocyte recruitment, resulting from diminished induction of adhesion molecules in the graft endothelium due to increased GATA2 SUMOylation...
June 1, 2017: Nature Communications
https://www.readbyqxmd.com/read/28562487/the-extracellular-matrix-in-ibd-a-dynamic-mediator-of-inflammation
#19
Aaron C Petrey, Carol A de la Motte
PURPOSE OF REVIEW: The extracellular matrix (ECM) is a frequently overlooked component of the pathogenesis of inflammatory bowel disease (IBD). However, the functional and clinically significant interactions between immune as well as nonimmune cells with the ECM have important implications for disease pathogenesis. In this review, we discuss how the ECM participates in process associated with IBD that involves diverse cell types of the intestine. RECENT FINDINGS: Remodeling of the ECM is a consistent feature of IBD, and studies have implicated key ECM molecules in IBD pathogenesis...
July 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28556377/deficiency-of-filaggrin-regulates-endogenous-cysteine-protease-activity-leading-to-impaired-skin-barrier-function
#20
X W Wang, J J Wang, D Gutowska-Owsiak, M Salimi, T A Selvakumar, A Gwela, L Y Chen, Y J Wang, E Giannoulatou, G Ogg
BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disorder, characterized by skin barrier defects and enhanced allergen priming. Null mutations in the filaggrin gene (FLG) are strongly associated with moderate to severe AD, but the pathways linking barrier dysfunction and cutaneous inflammation are still largely unknown. AIM: To assess alteration of endogenous cysteine protease activity in FLG-deficient keratinocytes, and to determine whether the alteration in cysteine protease activity affects epidermal barrier function and associated gene and protein expression...
May 29, 2017: Clinical and Experimental Dermatology
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