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Protease and inflammation

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https://www.readbyqxmd.com/read/29228786/oxidative-stress-induces-disruption-of-the-axon-initial-segment
#1
Kareem Clark, Brooke A Sword, Jeffrey L Dupree
The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear...
November 2017: ASN Neuro
https://www.readbyqxmd.com/read/29228045/mycobacterial-infection-induces-higher-interleukin-1%C3%AE-and-dysregulated-lung-inflammation-in-mice-with-defective-leukocyte-nadph-oxidase
#2
Wen-Cheng Chao, Chia-Liang Yen, Cheng-Yuan Hsieh, Ya-Fang Huang, Yau-Lin Tseng, Peter Andrija Nigrovic, Chi-Chang Shieh
Granulomatous inflammation causes severe tissue damage in mycobacterial infection while redox status was reported to be crucial in the granulomatous inflammation. Here, we used a NADPH oxidase 2 (NOX2)-deficient mice (Ncf1-/-) to investigate the role of leukocyte-produced reactive oxygen species (ROS) in mycobacterium-induced granulomatous inflammation. We found poorly controlled mycobacterial proliferation, significant body weight loss, and a high mortality rate after M. marinum infection in Ncf1-/- mice. Moreover, we noticed loose and neutrophilic granulomas and higher levels of interleukin (IL)-1β and neutrophil chemokines in Ncf1-/- mice when compared with those in wild type mice...
2017: PloS One
https://www.readbyqxmd.com/read/29219180/laminar-shear-stress-promotes-mitochondrial-homeostasis-in-endothelial-cells
#3
Li-Hong Wu, Hao-Chun Chang, Pei-Ching Ting, Danny Ling Wang
Vascular endothelial cells (ECs) are constantly subjected to flow-induced shear stress that is crucial for endothelial functions. Laminar shear stress (LSS) exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for cellular survival. However, the effects of LSS on mitochondrial homeostasis in ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined. Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm2 ) generated by a parallel-plate flow chamber system...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29218110/downregulation-of-cathepsin-g-reduces-the-activation-of-cd4-t-cells-in-murine-autoimmune-diabetes
#4
Fang Zou, Xiaoyang Lai, Jing Li, Shuihong Lei, Lei Hu
Type 1 diabetes mellitus (T1DM) is an autoimmune disease due to progressive injury of islet cells mediated by T lymphocytes (T cells). Our previous studies have shown that only cathepsin G (CatG), not other proteases, is involved in the antigen presentation of proinsulin, and if the presentation is inhibited, the activation of CD4+ T cells induced by proinsulin is alleviated in T1DM patients, and CatG-specific inhibitor reduces the activation of CD4+ cells induced by proinsulin in T1DM patients. Therefore, we hypothesize that CatG may play an important role in the activation of CD4+ T cells in T1DM...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29215061/local-production-of-activated-factor-x-in-atherosclerotic-plaque-induced-vascular-smooth-muscle-cell-senescence
#5
Fumihiro Sanada, Jun Muratsu, Rei Otsu, Hideo Shimizu, Nobutaka Koibuchi, Kazutaka Uchida, Yoshiaki Taniyama, Shinichi Yoshimura, Hiromi Rakugi, Ryuichi Morishita
Our previous study demonstrated that coagulation factor Xa (FXa) induced endothelial cell senescence, resulting in inflammation and impaired angiogenesis. This mechanism is dictated through protease-activated receptors, PARs, insulin-like growth factor-binding protein 5 (IGFBP-5), and p53. Activation of PARs contributes to the pathophysiology of several chronic inflammatory diseases, including atherosclerosis. Thus, we speculated that similar mechanism might participate in the progression of atherosclerotic plaques...
December 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29214073/assessment-of-ocriplasmin-effects-on-the-vitreoretinal-compartment-in-porcine-and-human-model-systems
#6
Bart Jonckx, Michael Porcu, Aurelie Candi, Isabelle Etienne, Philippe Barbeaux, Jean H M Feyen
Ocriplasmin (Jetrea®) is a recombinant protease used to treat vitreomacular traction. To gain insight into vitreoretinal observations reported after ocriplasmin treatment, we have developed an in vivo porcine ocriplasmin-induced posterior vitreous detachment (PVD) model in which we investigated vitreoretinal tissues by optical coherence tomography, histology, and cytokine profiling. Eight weeks postinjection, ocriplasmin yielded PVD in 82% of eyes. Subretinal fluid (85%) and vitreous hyperreflective spots (45%) were resolved by week 3...
2017: Journal of Ophthalmology
https://www.readbyqxmd.com/read/29212956/icam1-neutrophils-promote-chronic-inflammation-via-asprv1-in-b-cell-dependent-autoimmune-encephalomyelitis
#7
Ryder F Whittaker Hawkins, Alexandre Patenaude, Aline Dumas, Rajiv Jain, Yodit Tesfagiorgis, Steven Kerfoot, Takeshi Matsui, Matthias Gunzer, Patrice E Poubelle, Catherine Larochelle, Martin Pelletier, Luc Vallières
Neutrophils contribute to demyelinating autoimmune diseases, yet their phenotype and functions have been elusive to date. Here, we demonstrate that ICAM1 surface expression distinguishes extra- from intravascular neutrophils in the mouse CNS during experimental autoimmune encephalomyelitis (EAE). Transcriptomic analysis of these 2 subpopulations indicated that neutrophils, once extravasated, acquire macrophage-like properties, including the potential for immunostimulation and MHC class II-mediated antigen presentation...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29210131/allergens-produce-serine-proteases-dependent-distinct-release-of-metabolite-damps-in-human-bronchial-epithelial-cells
#8
Sangeetha Ramu, Mandy Menzel, Leif Bjermer, Cecilia Andersson, Hamid Akbarshahi, Lena Uller
BACKGROUND: The respiratory epithelium is a major site for disease interaction with inhaled allergens. Additional to IgE-dependent effects, allergens contain proteases that may stimulate human bronchial epithelial cells (HBECs) through protease-activated receptors, causing the release of mediators important in driving Th2 mediated immune responses. OBJECTIVE: We aimed to investigate if different allergens induce metabolite DAMPs such as ATP and uric acid (UA) release in HBECs...
December 6, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29209066/interaction-of-complement-defence-collagens-c1q-and-mannose-binding-lectin-with-bmp-1-tolloid-like-proteinases
#9
Monique Lacroix, Agnès Tessier, Chantal Dumestre-Pérard, Sandrine Vadon-Le Goff, Evelyne Gout, Leena Bruckner-Tuderman, Dimitra Kiritsi, Alexander Nyström, Sylvie Ricard-Blum, Catherine Moali, David J S Hulmes, Nicole M Thielens
The defence collagens C1q and mannose-binding lectin (MBL) are immune recognition proteins that associate with the serine proteinases C1r/C1s and MBL-associated serine proteases (MASPs) to trigger activation of complement, a major innate immune system. Bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases (BTPs) are metalloproteinases with major roles in extracellular matrix assembly and growth factor signalling. Despite their different functions, C1r/C1s/MASPs and BTPs share structural similarities, including a specific CUB-EGF-CUB domain arrangement found only in these enzymes that mediates interactions with collagen-like proteins, suggesting a possible functional relationship...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29201258/molecular-mechanisms-of-porphyromonas-gingivalis-host-cell-interaction-on-periodontal-diseases
#10
REVIEW
Masaaki Nakayama, Naoya Ohara
Porphyromonas gingivalis (P. gingivalis) is a major oral pathogen and associated with periodontal diseases including periodontitis and alveolar bone loss. In this review, we indicate that two virulence factors, which are hemoglobin receptor protein (HbR) and cysteine proteases "gingipains", expressed by P. gingivalis have novel functions on the pathogenicity of P. gingivalis. P. gingivalis produces three types of gingipains and concomitantly several adhesin domains. Among the adhesin domains, hemoglobin receptor protein (HbR), also called HGP15, has the function of induction of interleukin-8 (IL-8) expression in human gingival epithelial cells, indicating the possibility that HbR is associated with P...
November 2017: Japanese Dental Science Review
https://www.readbyqxmd.com/read/29199228/progression-of-time-dependent-changes-to-the-mechanisms-of-vasodilation-by-protease-activated-receptor-2-in-metabolic-syndrome
#11
Kana Maruyama, John J McGuire, Satomi Kagota
Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteases released from tissues or by synthetic peptide ligands administered pharmacologically. Its wide expression in the cardiovascular system, particularly within the endothelium, vasodilation activity, and link to increased expression of inflammatory cytokines positions PAR2 as a potentially important regulator of vascular pathology under conditions of tissue inflammation, and injury; and thus, a pharmaceutical target for new therapeutics...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29199140/physiological-functions-of-non-apoptotic-caspase-activity-in-the-nervous-system
#12
REVIEW
Emilie Hollville, Mohanish Deshmukh
Caspases are cysteine proteases that play important and well-defined roles in apoptosis and inflammation. Increasing evidence point to alternative functions of caspases where restricted and localized caspase activation within neurons allows for a variety of non-apoptotic and non-inflammatory processes required for brain development and function. In this review, we highlight sublethal caspase functions in axon and dendrite pruning, neurite outgrowth and dendrite branches formation, as well as in long-term depression and synaptic plasticity...
November 30, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29192497/identification-of-new-anti-inflammatory-peptides-from-zein-hydrolysate-after-simulated-gastrointestinal-digestion-and-transport-in-caco-2-cells
#13
Qiufang Liang, Meram Chalamaiah, Xiaofeng Ren, Haile Ma, Jianping Wu
Chronic inflammation is an underlying contributor to various chronic diseases. The objectives of this study were to investigate the anti-inflammatory activity of zein hydrolysate after simulated gastrointestinal digestion and Caco-2 cell absorption, and to identify novel anti-inflammatory peptides after transport across Caco-2 cells. Three zein hydrolysates were prepared and further digested using gastrointestinal proteases; their transports were studied in Caco-2 cells. Anti-inflammatory activity was studied in endothelial EA...
December 1, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29190292/tnf-%C3%AE-blockade-suppresses-pericystic-inflammation-following-anthelmintic-treatment-in-porcine-neurocysticercosis
#14
Siddhartha Mahanty, Miguel A Orrego, Carla Cangalaya, M Paz Adrianzen, Gianfranco Arroyo, Juan Calcina, Armando E Gonzalez, Héctor H García, Cristina Guerra-Giraldez, Theodore E Nash
BACKGROUND: Neurocysticercosis (NCC) is an infection of the brain with the larval cyst of the tapeworm, Taenia solium. Cysticidal treatment induces parasite killing resulting in a post inflammatory response and seizures, which generally requires corticosteroid treatment to control inflammation. The nature of this response and how to best control it is unclear. We investigated the anti-inflammatory effects of pretreatment with etanercept (ETN), an anti-tumor necrosis factor agent, or dexamethasone (DEX), a high potency corticosteroid, on the post treatment inflammatory response in naturally infected pigs with neurocysticercosis after a single dose of the cysticidal drug praziquantel (PZQ)...
November 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29181004/identification-of-secretory-leukoprotease-inhibitor-as-an-endogenous-negative-regulator-in-allergic-effector-cells
#15
Shintaro Matsuba, Toshiki Yabe-Wada, Kazuya Takeda, Tetsuya Sato, Mikita Suyama, Toshiyuki Takai, Toshiaki Kikuchi, Toshihiro Nukiwa, Akira Nakamura
Mast cells, basophils, and eosinophils are central effectors in allergic inflammatory disorders. These cells secrete abundant serine proteases as well as chemical mediators and cytokines; however, the expression profiles and functions of their endogenous inhibitors remain elusive. We found that murine secretory leukoprotease inhibitor (SLPI) is expressed in basophils and eosinophils but in not in mast cells. SLPI-deficient (Slpi-/-) basophils produce more cytokines than wild-type mice after IgE stimulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29178989/interaction-of-factor-vii-activating-protease-fsap-with-neutrophil-extracellular-traps-nets
#16
Simona Grasso, Ariane Neumann, Irene M Lang, Michael Etscheid, Maren von Köckritz-Blickwede, Sandip M Kanse
The circulating zymogen form of Factor VII activating protease (FSAP) can be activated by histones and nucleosomes in vivo. These cell-death-associated nuclear factors are also actively extruded into the extracellular space by neutrophils through a process called neutrophil extracellular trap (NET) formation (NETosis). NETs are thought to be involved in host defense, inflammation as well as thrombosis. We have investigated the bidirectional interactions of FSAP and NETs. Phorbol ester-mediated NET formation was marginally stimulated by FSAP...
November 21, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/29171765/serine-protease-inhibitors-to-treat-inflammation-a-patent-review-2011-2016
#17
Chahrazade El Amiri, Feryel Soualmia
Introduction Inflammation is a physiological part of the complex biological response of tissues to counteract various harmful signals. This process involves diverse actors such as immune cells, blood vessels, and nerves as sources of mediators for inflammation control. Among them serine proteases are key elements in both physiological and pathological inflammation. Areas covered Serine protease inhibitors to treat inflammatory diseases are being actively investigated by various industrial and academic institutions...
November 24, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29167233/granzyme-a-in-human-platelets-regulates-the-synthesis-of-proinflammatory-cytokines-by-monocytes-in-aging
#18
Robert A Campbell, Zechariah Franks, Anish Bhatnagar, Jesse W Rowley, Bhanu K Manne, Mark A Supiano, Hansjorg Schwertz, Andrew S Weyrich, Matthew T Rondina
Dysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream cytokine synthesis in aging remains poorly understood. Platelets and monocytes were isolated from healthy younger (age <45, n = 37) and older (age ≥65, n = 30) adults and incubated together under autologous and nonautologous conditions. Synthesis of inflammatory cytokines by monocytes, alone or in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging...
November 22, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29164814/a-thrombin-receptor-derived-imaging-agent-detects-subclinical-arthritis-in-mice
#19
Beth Friedman, Michael A Whitney, Elamprakash N Savariar, Christa Caneda, Paul Steinbach, Qing Xiong, Dina V Hingorani, Jessica Crisp, Stephen R Adams, Michael Kenner, Csilla N Lippert, Quyen T Nguyen, Monica Guma, Roger Y Tsien, Maripat Corr
OBJECTIVE: Functional imaging of synovitis could improve both early detection of rheumatoid arthritis (RA) and long-term outcomes. Motivated by the intersection of inflammation with coagulation protease activation, we examine coagulation protease activities in arthritic mice with a dual fluorescent Ratiometric thrombin-Activatable Cell Penetrating Peptide (RACPPNleTPRSFL ). METHOD: Mice with chronic transgenic K/BxN arthritis, or with arthritis on Day 1 of passive serum transfer induced arthritis (STIA), were imaged in vivo for Cy5 em: Cy7 em ratiometric fluorescence from proteolytic cleavage and activation of RACPPNleTPRSFL ...
November 22, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29162504/checks-and-balances-between-autophagy-and-the-inflammasomes-during-infection
#20
REVIEW
Stephanie Seveau, Joanne Turner, Mikhail A Gavrilin, Jordi B Torrelles, Luanne Hall-Stoodley, Jacob Yount, Amal O Amer
Autophagy and inflammasome complex assembly are physiological processes that control homeostasis, inflammation, and immunity. Autophagy is a ubiquitous pathway that degrades cytosolic macromolecules or organelles, as well as intracellular pathogens. Inflammasomes are multi-protein complexes that assemble in the cytosol of cells upon detection of pathogen- or danger-associated molecular patterns. A critical outcome of inflammasome assembly is the activation of the serine protease caspase-1, which activates the pro-inflammatory cytokine precursors pro-IL-1β and pro-IL-18...
November 18, 2017: Journal of Molecular Biology
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