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Cathepsin G

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https://www.readbyqxmd.com/read/28220120/neutrophil-extracellular-traps-and-its-implications-in-inflammation-an-overview
#1
REVIEW
Vidal Delgado-Rizo, Marco A Martínez-Guzmán, Liliana Iñiguez-Gutierrez, Alejandra García-Orozco, Anabell Alvarado-Navarro, Mary Fafutis-Morris
In addition to physical barriers, neutrophils are considered a part of the first line of immune defense. They can be found in the bloodstream, with a lifespan of 6-8 h, and in tissue, where they can last up to 7 days. The mechanisms that neutrophils utilize for host defense are phagocytosis, degranulation, cytokine production, and, the most recently described, neutrophil extracellular trap (NET) production. NETs are DNA structures released due to chromatin decondensation and spreading, and they thus occupy three to five times the volume of condensed chromatin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28212734/role-of-granule-proteases-in-the-life-and-death-of-neutrophils
#2
REVIEW
Charaf Benarafa, Hans-Uwe Simon
Neutrophils constitute a crucial component of the innate immune defenses against microbes. Produced in the bone marrow and patrolling in blood vessels, neutrophils are recruited to injured tissues and are immediately active to contain pathogen invasion. Neutrophils undergo programmed cell death by multiple, context-specific pathways, which have consequences on immunopathology and disease outcome. Studies in the last decade indicate additional functions for neutrophils - or a subset of neutrophils - in modulating adaptive responses and tumor progression...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28192517/neutrophils-and-neutrophil-serine-proteases-are-increased-in-the-spleens-of-estrogen-treated-c57bl-6-mice-and-several-strains-of-spontaneous-lupus-prone-mice
#3
Rujuan Dai, Catharine Cowan, Bettina Heid, Deena Khan, Zhihong Liang, Christine T N Pham, S Ansar Ahmed
Estrogen, a natural immunomodulator, regulates the development and function of diverse immune cell types. There is now renewed attention on neutrophils and neutrophil serine proteases (NSPs) such as neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CG) in inflammation and autoimmunity. In this study, we found that although estrogen treatment significantly reduced total splenocytes number, it markedly increased the splenic neutrophil absolute numbers in estrogen-treated C57BL/6 (B6) mice when compared to placebo controls...
2017: PloS One
https://www.readbyqxmd.com/read/28190401/rapid-transcriptional-plasticity-of-duplicated-gene-clusters-enables-a-clonally-reproducing-aphid-to-colonise-diverse-plant-species
#4
Thomas C Mathers, Yazhou Chen, Gemy Kaithakottil, Fabrice Legeai, Sam T Mugford, Patrice Baa-Puyoulet, Anthony Bretaudeau, Bernardo Clavijo, Stefano Colella, Olivier Collin, Tamas Dalmay, Thomas Derrien, Honglin Feng, Toni Gabaldón, Anna Jordan, Irene Julca, Graeme J Kettles, Krissana Kowitwanich, Dominique Lavenier, Paolo Lenzi, Sara Lopez-Gomollon, Damian Loska, Daniel Mapleson, Florian Maumus, Simon Moxon, Daniel R G Price, Akiko Sugio, Manuella van Munster, Marilyne Uzest, Darren Waite, Georg Jander, Denis Tagu, Alex C C Wilson, Cock van Oosterhout, David Swarbreck, Saskia A Hogenhout
BACKGROUND: The prevailing paradigm of host-parasite evolution is that arms races lead to increasing specialisation via genetic adaptation. Insect herbivores are no exception and the majority have evolved to colonise a small number of closely related host species. Remarkably, the green peach aphid, Myzus persicae, colonises plant species across 40 families and single M. persicae clonal lineages can colonise distantly related plants. This remarkable ability makes M. persicae a highly destructive pest of many important crop species...
February 13, 2017: Genome Biology
https://www.readbyqxmd.com/read/28187461/lysosomal-accumulation-of-anticancer-drugs-triggers-lysosomal-exocytosis
#5
Benny Zhitomirsky, Yehuda G Assaraf
We have recently shown that hydrophobic weak base anticancer drugs are highly sequestered in acidic lysosomes, inducing TFEB-mediated lysosomal biogenesis and markedly increased lysosome numbers per cell. This enhanced lysosomal sequestration of chemotherapeutics, away from their intracellular targets, provoked cancer multidrug resistance. However, little is known regarding the fate of lysosome-sequestered drugs. While we suggested that sequestered drugs might be expelled from cancer cells via lysosomal exocytosis, no actual drug-induced lysosomal exocytosis was demonstrated...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28168343/is-infection-the-possible-initiator-of-disc-disease-an-insight-from-proteomic-analysis
#6
S Rajasekaran, Chitraa Tangavel, Siddharth N Aiyer, Sharon Miracle Nayagam, M Raveendran, Naveen Luke Demonte, Pramela Subbaiah, Rishi Kanna, Ajoy Prasad Shetty, K Dharmalingam
STUDY DESIGN: Proteomic and 16S rDNA analysis of disc tissues obtained in vivo. OBJECTIVE: To address the controversy of infection as an aetiology for disc disorders through protein profiling. There is raging controversy over the presence of bacteria in human lumbar discs in vivo, and if they represent contamination or infection. Proteomics can provide valuable insight by identifying proteins signifying bacterial presence and, also host defence response proteins (HDRPs), which will confirm infection...
February 6, 2017: European Spine Journal
https://www.readbyqxmd.com/read/28164558/increased-number-of-mast-cells-in-atherosclerotic-lesions-correlates-with-the-presence-of-myeloid-but-not-plasmacytoid-dendritic-cells-as-well-as-pro-inflammatory-t-cells
#7
Ilonka Rohm, Sandra Sattler, Yevgeniya Atiskova, Daniel Kretzschmar, Rudin Pistulli, Marcus Franz, Christian Jung, Gita Mall, Thomas Kronert, Paul C Schulze, Atilla Yilmaz
BACKGROUND: Atherosclerosis is an inflammatory disease of the vessel wall promoted by different immune cells and inflammatory mediators. METHODS: In this study, 26 human plaques and 12 control vessels without atherosclerosis were immunohistochemically stained to analyze the emergence of mast cells dependent on plaque morphology and to correlate mast cell occurrence with the emergence of myeloid as well as plasmacytoid dendritic cells. Also, mast cell emergence was correlated with the number of pro-inflammatory T cells...
December 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28152632/cervical-fluid-calreticulin-and-cathepsin-g-in-pregnancies-complicated-by-preterm-prelabor-rupture-of-membranes
#8
Ctirad Andrys, Ivana Musilova, Marcela Drahosova, Ondrej Soucek, Lenka Pliskova, Bo Jacobsson, Nanbert Zhong, Marian Kacerovsky
OBJECTIVE: The study aimed to determine the cervical calreticulin and cathepsin-G concentrations in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI). METHODS: Eighty women with singleton pregnancies complicated by PPROM were included in this study. Cervical and amniotic fluids were obtained at the time of admission, and concentrations of calreticulin and cathepsin-G in cervical fluid were determined using ELISA...
February 2, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28139439/neutrophil-protease-cleavage-of-von-willebrand-factor-in-glomeruli-an-anti-thrombotic-mechanism-in-the-kidney
#9
Ramesh Tati, Ann-Charlotte Kristoffersson, Minola Manea Hedström, Matthias Mörgelin, Jörgen Wieslander, Cees van Kooten, Diana Karpman
Adequate cleavage of von Willebrand factor (VWF) prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM) was studied as a reflection of processes occurring in the subendothelial glomerular space...
January 24, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28137252/enhanced-transcriptomic-responses-in-the-pacific-salmon-louse-lepeophtheirus-salmonis-oncorhynchi-to-the-non-native-atlantic-salmon-salmo-salar-suggests-increased-parasite-fitness
#10
Laura M Braden, Ben J G Sutherland, Ben F Koop, Simon R M Jones
BACKGROUND: Outcomes of infections with the salmon louse Lepeophtheirus salmonis vary considerably among its natural hosts (Salmo, Oncorhynchus spp.). Host-parasite interactions range from weak to strong host responses accompanied by high to low parasite abundances, respectively. Parasite behavioral studies indicate that the louse prefers the host Atlantic Salmon (Salmo salar), which is characterized by a weak immune response, and that this results in enhanced parasite reproduction and growth rates...
January 30, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28129394/characterization-of-early-phase-neutrophil-extracellular-traps-in-urinary-tract-infections
#11
Yanbao Yu, Keehwan Kwon, Tamara Tsitrin, Shiferaw Bekele, Patricia Sikorski, Karen E Nelson, Rembert Pieper
Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28118364/physical-and-flavor-characteristics-fatty-acid-profile-antioxidant-status-and-nrf2-dependent-antioxidant-enzyme-gene-expression-changes-in-young-grass-carp-ctenopharyngodon-idella-fillets-fed-dietary-valine
#12
Jian-Bo Luo, Lin Feng, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study was conducted to examine the effects of dietary valine on the physical and flavor characteristics, fatty acid (FA) profile, antioxidant status and Nrf2-dependent antioxidant enzyme gene expression in the muscle of young grass carp (Ctenopharyngodon idella) fed increasing levels of valine (4.3, 8.0, 10.6, 13.1, 16.9 and 19.1 g/kg) for 8 weeks. Compared with the control group, the group fed valine showed improved physical characteristics of fish fillets (increased relative shear force, hydroxyproline, protein and lipid levels and decreased cathepsin B and L activities, as well as cooking loss, were observed)...
2017: PloS One
https://www.readbyqxmd.com/read/28117205/synthesis-and-biological-evaluation-of-a-water-soluble-phosphate-prodrug-salt-and-structural-analogues-of-kgp94-a-lead-inhibitor-of-cathepsin-l
#13
Erica N Parker, Samuel O Odutola, Yifan Wang, Tracy E Strecker, Rajeswari Mukherjee, Zhe Shi, David J Chaplin, Mary Lynn Trawick, Kevin G Pinney
The magnitude of expression of cathepsin L, often upregulated in the tumor microenvironment, correlates with the invasive and metastatic nature of certain tumors. Inhibition of cathepsin L represents an emerging strategy for the treatment of metastatic cancer. A potent, small-molecule inhibitor (referred to as KGP94) of cathepsin L, and new KGP94 analogues were synthesized. (3,5-Dibromophenyl)-(3-hydroxyphenyl) ketone thiosemicarbazone (22), with an IC50 value of 202nM, exhibited similar inhibitory activity against cathepsin L compared to KGP94 (IC50=189nM)...
December 21, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28104604/hiv-infection-model-of-chronic-obstructive-pulmonary-disease-in-mice
#14
Patrick Geraghty, Eran Hadas, Boe-Hyun Kim, Abdoulaye J Dabo, David J Volsky, Robert Foronjy
Cigarette smoke usage is prevalent in HIV+ patients and, despite highly active antiretroviral therapy (HAART), these individuals develop an accelerated form of chronic obstructive pulmonary disease (COPD). Studies investigating the mechanisms of COPD development in HIV have been limited by the lack of suitable mouse models. Here we describe a model of HIV induced COPD in wild type mice using EcoHIV, a chimeric HIV capable of establishing chronic infection in immunocompetent mice. A/J mice were infected with EcoHIV and subjected to whole body cigarette smoke exposure...
January 19, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28103268/direct-observation-of-enhanced-nitric-oxide-in-a-murine-model-of-diabetic-nephropathy
#15
Margien G S Boels, Ernst E H van Faassen, M Cristina Avramut, Johan van der Vlag, Bernard M van den Berg, Ton J Rabelink
Uncoupling of nitric oxide synthase (NOS) secondary to redox signaling is a central mechanism in endothelial and macrophage activation. To date studies on the production of nitric oxide (NO) during the development of diabetic complications show paradoxical results. We previously showed that recoupling eNOS by increasing the eNOS cofactor tetrahydrobiopterin (BH4) could restore endothelial function and prevent kidney injury in experimental kidney transplantation. Here, we employed a diabetic mouse model to investigate the effects of diabetes on renal tissue NO bioavailability...
2017: PloS One
https://www.readbyqxmd.com/read/28073925/progranulin-regulates-lysosomal-function-and-biogenesis-through-acidification-of-lysosomes
#16
Yoshinori Tanaka, Genjiro Suzuki, Takashi Matsuwaki, Masato Hosokawa, Geidy Serrano, Thomas G Beach, Keitaro Yamanouchi, Masato Hasegawa, Masugi Nishihara
Progranulin (PGRN) haploinsufficiency resulting from loss-of-function mutations in the PGRN gene causes frontotemporal lobar degeneration accompanied by TDP-43 accumulation, and patients with homozygous mutations in the PGRN gene present with neuronal ceroid lipofuscinosis. Although it remains unknown why PGRN deficiency causes neurodegenerative diseases, there is increasing evidence that PGRN is implicated in lysosomal functions. Here, we show PGRN is a secretory lysosomal protein that regulates lysosomal function and biogenesis by controlling the acidification of lysosomes...
January 10, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28062798/quantitative-proteome-analysis-of-mouse-liver-lysosomes-provides-evidence-for-mannose-6-phosphate-independent-targeting-mechanisms-of-acid-hydrolases-in-mucolipidosis-ii
#17
Sandra Markmann, Svenja Krambeck, Christopher J Hughes, Mina Mirzaian, Johannes M F G Aerts, Paul Saftig, Michaela Schweizer, Johannes C P Vissers, Thomas Braulke, Markus Damme
The efficient receptor-mediated targeting of soluble lysosomal proteins to lysosomes requires the modification with mannose 6-phosphate (M6P) residues. Although the absence of M6P results in missorting and hypersecretion of lysosomal enzymes in many cells, normal levels of lysosomal enzymes have been reported in liver of patients lacking the M6P-generating phosphotransferase (PT). The identity of lysosomal proteins depending on M6P has not yet been comprehensively analyzed. In this study we purified lysosomes from liver of PT-defective mice and 67 known soluble lysosomal proteins were quantified using an ion mobility-assisted data independent label-free LC-MS approach...
January 6, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28053237/highly-selective-cleavage-of-cytokines-and-chemokines-by-the-human-mast-cell-chymase-and-neutrophil-cathepsin-g
#18
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/28045523/design-of-potent-and-selective-cathepsin-g-inhibitors-based-on-the-sunflower-trypsin-inhibitor-1-scaffold
#19
Joakim E Swedberg, Choi Yi Li, Simon J de Veer, Conan K Wang, David J Craik
Neutrophils are directly responsible for destroying invading pathogens via reactive oxygen species, antimicrobial peptides, and neutrophil serine proteases (NSPs). Imbalance between NSP activity and endogenous protease inhibitors is associated with chronic inflammatory disorders, and engineered inhibitors of NSPs are a potential therapeutic pathway. In this study we characterized the extended substrate specificity (P4-P1) of the NSP cathepsin G using a peptide substrate library. Substituting preferred cathepsin G substrate sequences into sunflower trypsin inhibitor-1 (SFTI-1) produced a potent cathepsin G inhibitor (Ki = 0...
January 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28043870/il-1-and-il-36-are-dominant-cytokines-in-generalized-pustular-psoriasis
#20
Andrew Johnston, Xianying Xing, Liza Wolterink, Drew H Barnes, ZhiQiang Yin, Laura Reingold, J Michelle Kahlenberg, Paul W Harms, Johann E Gudjonsson
BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, debilitating, and often life-threatening inflammatory disease characterized by episodic infiltration of neutrophils into the skin, pustule development, and systemic inflammation, which can manifest in the presence or absence of chronic plaque psoriasis (PV). Current treatments are unsatisfactory and warrant a better understanding of GPP pathogenesis. OBJECTIVE: We sought to understand better the disease mechanism of GPP to allow improved targeted therapies...
December 31, 2016: Journal of Allergy and Clinical Immunology
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