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Protease and inflammation

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https://www.readbyqxmd.com/read/29455535/antioxidative-nanoparticles-significantly-enhance-therapeutic-efficacy-of-an-antibacterial-therapy-against-listeria-monocytogenes-infection
#1
Yutaka Ikeda, Kazuhiro Shoji, Chitho P Feliciano, Shinji Saito, Yukio Nagasaki
Acute inflammatory conditions such as sepsis lead to fatal conditions, including multiple organ failure. Several treatments such as steroidal anti-inflammatory drugs are currently being investigated in order to decrease the blood cytokine level, which increases remarkably. However, any of these therapeutic treatments are not always reliable and effective; none have drastically improved survival rates, and some have mostly ended with failure. Reactive oxygen species (ROS) are signaling molecules responsible for the production of cytokines and chemokines that can mediate hyperactivation of the immune response called cytokine storm...
February 20, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29454835/mast-cells-signal-their-importance-in-health-and-disease
#2
EDITORIAL
Ana Olivera, Michael A Beaven, Dean D Metcalfe
FcεRI is the primary receptor in mast cells that mediate allergic reactions by inducing rapid release of mediators, an adaptive immune response that may have evolved as a host defense against parasites and venoms. Yet, it is apparent that mast cells are also activated via non-IgE receptors whose significance is just beginning to be understood. This includes the Mas-related GPCRs (MRGPRX2) that may contribute to reactions to diverse antimicrobials and polybasic compounds, and ADGRE2, an adhesion GPCR which is activated by mechanical vibration and whose variants are associated with familial vibratory urticaria...
February 15, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29454581/emerging-roles-of-microglial-cathepsins-in-neurodegenerative-disease
#3
REVIEW
Jessica R Lowry, Andis Klegeris
Alzheimer's disease (AD) is one of the leading causes of dementia, and its prevalence is expected to increase dramatically due to the aging global population. Microglia-driven neuroinflammation may contribute to the progression of AD. Microglia, the immune cells of the central nervous system (CNS), become chronically activated by the pathological proteins of AD including amyloid-β peptides (Aβ). Such adversely activated microglia secrete mediators that promote inflammation and damage neurons. Cathepsins are proteases that are expressed by all brain cell types, and most of them are found both intra- and extra-cellularly...
February 15, 2018: Brain Research Bulletin
https://www.readbyqxmd.com/read/29444464/transcriptional-profiling-molecular-cloning-and-functional-analysis-of-c1-inhibitor-the-main-regulator-of-the-complement-system-in-black-rockfish-sebastes-schlegelii
#4
Jehanathan Nilojan, S D N K Bathige, W S Thulasitha, Hyukjae Kwon, Sumi Jung, Myoung-Jin Kim, Bo-Hye Nam, Jehee Lee
C1-inhibitor (C1inh) plays a crucial role in assuring homeostasis and is the central regulator of the complement activation involved in immunity and inflammation. A C1-inhibitor gene from Sebastes schlegelii was identified and designated as SsC1inh. The identified genomic DNA and cDNA sequences were 6837 bp and 2161 bp, respectively. The genomic DNA possessed 11 exons, interrupted by 10 introns. The amino acid sequence possessed two immunoglobulin-like domains and a serpin domain. Multiple sequence alignment revealed that the serpin domain of SsC1inh was highly conserved among analyzed species where the two immunoglobulin-like domains showed divergence...
February 11, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29443899/protease-activated-receptor-4-par4-a-promising-target-for-antiplatelet-therapy
#5
REVIEW
Gamariel Rwibasira Rudinga, Ghulam Jilany Khan, Yi Kong
Cardiovascular diseases (CVDs) are currently among the leading causes of death worldwide. Platelet aggregation is a key cellular component of arterial thrombi and major cause of CVDs. Protease-activated receptors (PARs), including PAR1, PAR2, PAR3 and PAR4, fall within a subfamily of seven-transmembrane G-protein-coupled receptors (GPCR). Human platelets express PAR1 and PAR4, which contribute to the signaling transduction processes. In association with CVDs, PAR4 not only contributes to platelet activation but also is a modulator of cellular responses that serve as hallmarks of inflammation...
February 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29442501/exploiting-the-s4-s5-specificity-of-human-neutrophil-proteinase-3-to-improve-the-potency-of-peptidyl-di-chlorophenyl-phosphonate-ester-inhibitors-a-kinetic-and-molecular-modeling-analysis
#6
Carla Guarino, Natalia Gruba, Renata Grzywa, Edyta Dyguda-Kazimierowicz, Yveline Hamon, Monika Legowska, Marcin Skoreński, Sandrine Dallet-Choisy, Sylvain Marchand-Adam, Christine Kellenberger, Dieter E Jenne, Marcin Sieńczyk, Adam Lesner, Francis Gauthier, Brice Korkmaz
The neutrophilic serine protease proteinase 3 (PR3) is involved in inflammation and immune response and thus appears as a therapeutic target for a variety of infectious and inflammatory diseases. Here we combined kinetic and molecular docking studies to increase the potency of peptidyl-diphenyl phosphonate PR3 inhibitors. Occupancy of the S1 subsite of PR3 by a nVal residue and of the S4-S5 subsites by a biotinylated Val residue as obtained in biotin-VYDnVP(O-C6H4-4-Cl)2 enhanced the second order inhibition constant kobs/[I] towards PR3 by more than ten times (kobs/[I] = 73...
February 14, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29438939/at-rvd1-repairs-mouse-lung-after-cigarette-smoke-induced-emphysema-via-downregulation-of-oxidative-stress-by-nrf2-keap1-pathway
#7
Sara Vergel Posso, Nicolas Quesnot, João Alfredo Moraes, Lycia Brito-Gitirana, Emanuel Kennedy-Feitosa, Marina Valente Barroso, Luís Cristóvão Porto, Manuella Lanzetti, Samuel Santos Valença
Long-term exposure to cigarette smoke (CS) results in alveolar parenchyma destruction due to chronic inflammatory response and the imbalance between oxidants and antioxidants, and proteases and antiproteases. Emphysema is the main symptom of chronic obstructive pulmonary disease. Current treatment focuses on relieving respiratory symptoms, and inflammation resolution failure is an important pathophysiological element of the disease. Specialized pro-resolving mediators (SPMs) synthesized endogenously during resolution processes demonstrated beneficial effects in murine models of airway inflammation...
February 10, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29437593/%C3%AE-1-antitrypsin-infusion-for-treatment-of-steroid-resistant-acute-graft-versus-host-disease
#8
John M Magenau, Steven C Goldstein, Dan Peltier, Robert J Soiffer, Thomas Braun, Attaphol Pawarode, Mary M Riwes, Maggi Kennel, Joseph H Antin, Corey S Cutler, Vincent T Ho, Edwin P Alyea, Brian L Parkin, Gregory A Yanik, Sung Won Choi, Eli C Lewis, Charles A Dinarello, John Koreth, Pavan Reddy
Corticosteroid resistance following acute GVHD (SR-aGVHD) results in high morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Current immunosuppressive therapies for SR-aGVHD provide marginal effectiveness due to poor response or excessive toxicity, primarily from infection. Alpha-1 antitrypsin (AAT), a naturally abundant serine protease inhibitor, is capable of suppressing experimental GVHD by down-modulation of inflammation and increasing ratios of regulatory to effector T cells...
February 2, 2018: Blood
https://www.readbyqxmd.com/read/29434796/adam-proteases-involved-in-inflammation-are-differentially-altered-in-patients-with-gastritis-or-ulcer
#9
Nuray Erin, Sema Türker, Özlem Elpek, Bülent Yildirim
ADAM metallopeptidase domain (ADAM)9, 10 and 17 have α-secretase activity that regulates ectodomain shedding of factors involved in inflammation, cell proliferation, angiogenesis, and wound healing. The secretase activity of ADAM proteins is known to induce an inflammatory response. However, under certain conditions, a lack of secretase activity may induce inflammation suggesting differential roles of ADAM proteins with secretase activity. To the best of our knowledge, the present study evaluated the changes in α-secretase activity and expression of associated ADAM proteases (ADAM9, 10 and 17) in the gastric mucosa of patients with gastritis and ulcers, for the first time...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434599/rna-seq-analysis-of-il-1b-and-il-36-responses-in-epidermal-keratinocytes-identifies-a-shared-myd88-dependent-gene-signature
#10
William R Swindell, Maria A Beamer, Mrinal K Sarkar, Shannon Loftus, Joseph Fullmer, Xianying Xing, Nicole L Ward, Lam C Tsoi, Michelle J Kahlenberg, Yun Liang, Johann E Gudjonsson
IL-36 cytokines have recently emerged as mediators of inflammation in autoimmune conditions including psoriasis vulgaris (PsV) and generalized pustular psoriasis (GPP). This study used RNA-seq to profile the transcriptome of primary epidermal keratinocytes (KCs) treated with IL-1B, IL-36A, IL-36B, or IL-36G. We identified some early IL-1B-specific responses (8 h posttreatment), but nearly all late IL-1B responses were replicated by IL-36 cytokines (24 h posttreatment). Type I and II interferon genes exhibited time-dependent response patterns, with early induction (8 h) followed by no response or repression (24 h)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29433391/p-coumaric-acid-a-major-active-compound-of-bambusae-caulis-in-taeniam-suppresses-cigarette-smoke-induced-pulmonary-inflammation
#11
Woogyeong Kim, Dahae Lim, Jinju Kim
[Formula: see text]-coumaric acid ([Formula: see text]-CA) is a common compound found in medicinal herbs, including Bambusae Caulis in Taeniam (BC). It has been used to treat various diseases in China and Korea. Our previous study demonstrated that BC inhibits pulmonary and intestinal inflammation. In the present study, we used cigarette smoke (CS) to induce lung inflammation in vivo, and investigated the anti-inflammatory effects of [Formula: see text]-CA on CS-induced inflammatory mice model. Mice were treated with BC and [Formula: see text]-CA via oral injection 2[Formula: see text]h before CS exposure...
February 12, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29431207/role-of-mast-cells-and-basophils-in-pruritus
#12
REVIEW
Martin Steinhoff, Jörg Buddenkotte, Ethan A Lerner
To protect our body systems, there is a constant interactive conversation between the skin nervous and immune system. Important elements of this conversation in the skin include mast cells, basophils, and sensory nerve fibers. These cells employ a vast array of sensors that detect danger and react accordingly. This reaction, summarized as neurogenic inflammation, manifests at the conscious level as sensations including pain and itch. Here we provide a perspective on the blossoming knowledge that is illuminating connections between mast cells, basophils, and sensory nerve fibers in the mediation of itch...
March 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29430226/a-hepatitis-c-virus-associated-chronic-hepatitis-patient-developing-various-adverse-events-including-severe-gingivitis-gingival-bleeding-and-inflammation-of-genital-vulva-during-the-course-of-antiviral-therapy-with-elbasvir-grazoprevir
#13
Kazuo Tarao, Akira Sato
Oral direct-acting antivirals comprise the main therapy for hepatitis C virus (HCV)-associated liver disease in Japan. Daclatasvir/asunaprevir is the primary agent and sofosbuvir/ledipasvir is the secondary agent for HCV genotype 1b. Ombitasvir/paritaprevir/ritonavir was also recommended as a therapy for HCV genotype 1b. More recently, elbasvir (NS5A inhibitor)/grazoprevir (NS3/4A protease inhibitor) was also recommended as a potent therapy for HCV genotype 1b infection. This agent achieved an SVR12 as high as 96...
September 2017: Case Reports in Gastroenterology
https://www.readbyqxmd.com/read/29429965/mast-cells-promote-small-bowel-cancer-in-a-tumor-stage-specific-and-cytokine-dependent-manner
#14
Abdulrahman M Saadalla, Abu Osman, Michael F Gurish, Kristen L Dennis, Nichole R Blatner, Abdulmohammad Pezeshki, Kelly M McNagny, Hilde Cheroutre, Fotini Gounari, Khashayarsha Khazaie
Mast cells (MCs) are tissue resident sentinels that mature and orchestrate inflammation in response to infection and allergy. While they are also frequently observed in tumors, the contribution of MCs to carcinogenesis remains unclear. Here, we show that sequential oncogenic events in gut epithelia expand different types of MCs in a temporal-, spatial-, and cytokine-dependent manner. The first wave of MCs expands focally in benign adenomatous polyps, which have elevated levels of IL-10, IL-13, and IL-33, and are rich in type-2 innate lymphoid cells (ILC2s)...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29428221/the-inflammatory-microenvironment-that-promotes-gastrointestinal-cancer-development-and-invasion
#15
REVIEW
Kanae Echizen, Hiroko Oshima, Mizuho Nakayama, Masanobu Oshima
Accumulating evidence has indicated that the inflammatory response is important for tumor promotion. However, the mechanisms underlying the induction of the inflammatory response in cancer tissues and how it promotes tumorigenesis remain poorly understood. We constructed several mouse models that develop inflammation-associated gastric and intestinal tumors and examined the in vivo mechanisms of tumorigenesis. Of note, the activation of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) pathway and Toll-like receptor (TLR)/MyD88 signaling cooperatively induced the generation of an inflammatory microenvironment, which is required for early-stage tumorigenesis...
February 5, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29426602/airway-inflammation-after-epicutaneous-sensitization-of-mice-requires-protease-activity-of-low-dose-allergen-inhalation
#16
Izumi Nishioka, Toshiro Takai, Natsuko Maruyama, Seiji Kamijo, Punyada Suchiva, Mayu Suzuki, Shinya Kunimine, Hirono Ochi, Sakiko Shimura, Katsuko Sudo, Hideoki Ogawa, Ko Okumura, Shigaku Ikeda
No abstract text is available yet for this article.
January 31, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29425465/excess-mucin-impairs-subglottic-epithelial-host-defense-in-mechanically-ventilated-patients
#17
Jason Powell, James Garnett, Michael W Mather, Faye A H Cooles, Andrew Nelson, Bernard Verdon, Jon Scott, Kasim Jiwa, Marie-Hélène Ruchaud-Sparagano, Stephen P Cummings, John D Perry, Stephen E Wright, Janet A Wilson, Jeffrey Pearson, Chris Ward, A John Simpson
RATIONALE: Aspiration of infective subglottic secretions causes ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Mechanisms underlying subglottic colonization in critical illness have not been defined, limiting strategies for targeted prevention of VAP. OBJECTIVES: To characterize subglottic host defense dysfunction in mechanically ventilated patients in the intensive care unit (ICU). To determine whether subglottic mucin contributes to neutrophil phagocytic impairment and bacterial growth...
February 9, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29425229/schistosoma-mansoni-smki-1-serine-protease-inhibitor-binds-to-elastase-and-impairs-neutrophil-function-and-inflammation
#18
Suellen B Morais, Barbara C Figueiredo, Natan R G Assis, Debora M Alvarenga, Mariana T Q de Magalhães, Rafaela S Ferreira, Angélica T Vieira, Gustavo B Menezes, Sergio C Oliveira
Protease inhibitors have important function during homeostasis, inflammation and tissue injury. In this study, we described the role of Schistosoma mansoni SmKI-1 serine protease inhibitor in parasite development and as a molecule capable of regulating different models of inflammatory diseases. First, we determine that recombinant (r) SmKI-1 and its Kunitz domain but not the C-terminal region possess inhibitory activity against trypsin and neutrophil elastase (NE). To better understand the molecular basis of NE inhibition by SmKI-1, molecular docking studies were also conducted...
February 9, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29415890/thrombospondin-1-protects-against-pathogen-induced-lung-injury-by-limiting-extracellular-matrix-proteolysis
#19
Yanyan Qu, Tolani Olonisakin, William Bain, Jill Zupetic, Rebecca Brown, Mei Hulver, Zeyu Xiong, Jesus Tejero, Robert Mq Shanks, Jennifer M Bomberger, Vaughn S Cooper, Michael E Zegans, Hyunryul Ryu, Jongyoon Han, Joseph Pilewski, Anuradha Ray, Zhenyu Cheng, Prabir Ray, Janet S Lee
Acute lung injury is characterized by excessive extracellular matrix proteolysis and neutrophilic inflammation. A major risk factor for lung injury is bacterial pneumonia. However, host factors that protect against pathogen-induced and host-sustained proteolytic injury following infection are poorly understood. Pseudomonas aeruginosa (PA) is a major cause of nosocomial pneumonia and secretes proteases to amplify tissue injury. We show that thrombospondin-1 (TSP-1), a matricellular glycoprotein released during inflammation, dose-dependently inhibits PA metalloendoprotease LasB, a virulence factor...
February 8, 2018: JCI Insight
https://www.readbyqxmd.com/read/29414673/evolving-targets-for-the-treatment-of-atherosclerosis
#20
REVIEW
Ankita Solanki, Lokesh Kumar Bhatt, Thomas P Johnston
Atherosclerosis is a progressive disease of large arteries and a leading cause of cardiovascular diseases and stroke. Chronic inflammation, aberrant immune response, and disturbances to key enzymes involved with lipid metabolism are characteristic features of atherosclerosis. Apart from targeting the derangements in lipid metabolism, therapeutic modulation to regulate chronic inflammation and the immune system response may prove to be very promising strategies in the management of atherosclerosis. In recent years, various targets have been studied for the treatment of atherosclerosis...
February 4, 2018: Pharmacology & Therapeutics
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