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Protease and inflammation

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https://www.readbyqxmd.com/read/28820612/the-potential-of-signal-peptide-peptidase-as-a-therapeutic-target-for-hepatitis-c
#1
Kohji Moriishi
Chronic infection with hepatitis C virus (HCV) causes liver steatosis, cirrhosis, metabolic syndrome with inflammation, and eventually leads to hepatocellular carcinoma. HCV core protein is a well-known capsid protein and pathogenic factor related to lipid accumulation, type 2 diabetes mellitus, and carcinogenesis. Cleavage of the C-terminal transmembrane region by signal peptide peptidase (SPP) is required for maturation of the core protein. Areas covered: Herein, this review details the general aspects of the structure, lifecycle, pathogenesis, and maturation of the HCV core protein, the function of SPP, and clinically available direct-acting antivirals (DAAs)...
August 18, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28819304/novel-stat-binding-elements-mediate-il-6-regulation-of-mmp-1-and-mmp-3
#2
Samuel J Cutler, James D Doecke, Ibtisam Ghazawi, Jinbo Yang, Lyn R Griffiths, Kevin J Spring, Stephen J Ralph, Albert S Mellick
Dynamic remodelling of the extracellular matrix (ECM) is a key feature of cancer progression. Enzymes that modify the ECM, such as matrix metalloproteinases (MMPs), have long been recognised as important targets of anticancer therapy. Inflammatory cytokines are known to play a key role in regulating protease expression in cancer. Here we describe the identification of gamma-activated site (GAS)-like, signal transducer and activator of transcription (STAT) binding elements (SBEs) within the proximal promoters of the MMP-1 and MMP-3 genes, which in association with AP-1 components (c-Fos or Jun), bind STAT-1 in a homodimer like complex (HDLC)...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28815423/backbone-and-side-chain-1-h-15-n-and-13-c-resonance-assignments-of-a-novel-staphylococcal-inhibitor-of-myeloperoxidase
#3
Nicoleta T Ploscariu, Alvaro I Herrera, Srinivas Jayanthi, Thallapuranam K Suresh Kumar, Brian V Geisbrecht, Om Prakash
The bacterium Staphylococcus aureus produces an array of anti-inflammatory molecules that prevent the innate immune system from recognizing it as a pathogen and clearing it from the host. In the acute phase of inflammation, our immune system relies on neutrophils to clear invading bacteria. Recently, novel classes of secreted proteins from S. aureus, including the Extracellular Adherence Protein (EAP) family (Stapels et al., Proc Natl Acad Sci USA 111:13187-13192, 2014) and the Staphylococcal Peroxidase Inhibitor (SPIN), (unpublished work) have been identified as highly selective inhibitors acting on Neutrophil Serine Proteases (NSPs) and myeloperoxidase (MPO) respectively...
August 16, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28811549/diagnosing-peri-implant-disease-using-the-tongue-as-a-24-7-detector
#4
J Ritzer, T Lühmann, C Rode, M Pein-Hackelbusch, I Immohr, U Schedler, T Thiele, S Stübinger, B V Rechenberg, J Waser-Althaus, F Schlottig, M Merli, H Dawe, M Karpíšek, R Wyrwa, M Schnabelrauch, L Meinel
Our ability of screening broad communities for clinically asymptomatic diseases critically drives population health. Sensory chewing gums are presented targeting the tongue as 24/7 detector allowing diagnosis by "anyone, anywhere, anytime". The chewing gum contains peptide sensors consisting of a protease cleavable linker in between a bitter substance and a microparticle. Matrix metalloproteinases in the oral cavity, as upregulated in peri-implant disease, specifically target the protease cleavable linker while chewing the gum, thereby generating bitterness for detection by the tongue...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28808241/specific-calpain-inhibition-protects-kidney-against-inflammaging
#5
Guillaume Hanouna, Laurent Mesnard, Sophie Vandermeersch, Joëlle Perez, Sandrine Placier, Jean-Philippe Haymann, Fabien Campagne, Julien Moroch, Aurélien Bataille, Laurent Baud, Emmanuel Letavernier
Calpains are ubiquitous pro-inflammatory proteases, whose activity is controlled by calpastatin, their specific inhibitor. Transgenic mice over-expressing rabbit calpastatin (CalpTG) are protected against vascular remodelling and angiotensin II-dependent inflammation. We hypothesized that specific calpain inhibition would protect against aging-related lesions in arteries and kidneys. We analysed tissues from 2-months and 2-years-old CalpTG and wild-type mice and performed high throughput RNA-Sequencing of kidney tissue in aged mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808141/a-critical-role-for-plasma-kallikrein-in-the-pathogenesis-of-autoantibody-induced-arthritis
#6
Aizhen Yang, Junsong Zhou, Bo Wang, Jihong Dai, Robert W Colman, Wenchao Song, Yi Wu
The plasma kallikrein-kinin system (KKS) consists of serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-MW kininogen (HK). Upon activation, activated pKal and FXII cleave HK to release bradykinin. Activation of this system has been noted in patients with rheumatoid arthritis, and its pathogenic role has been characterized in animal arthritic models. In this study, we generated 2 knockout mouse strains that lacked pKal and HK and determined the role of KKS in autoantibody-induced arthritis...
August 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28805938/what-is-new-in-the-pathophysiology-of-acne-an-overview
#7
REVIEW
B Dréno
Acne is a chronic inflammatory disease of the pilosebaceous unit. Its pathophysiology includes hyperseborrhoea, abnormal follicular keratinization and Propionibacterium acnes proliferation in the pilosebaceous unit. Recent research has shed some new light on the involvement of the sebaceous gland, as well as on the pro-inflammatory activity of the cutaneous microbiome. During puberty, alteration of the sebaceous lipid profile, called dysseborrhoea, stress, irritation, cosmetics and potential dietary factors lead to inflammation and formation of different types of acne lesions...
September 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28793333/media-from-macrophages-co-incubated-with-enterococcus-faecalis-induces-epithelial-cell-monolayer-reassembly-and-altered-cell-morphology
#8
Natalia Belogortseva, Monika Krezalek, Kristina Guyton, Christine Labno, Valeriy Poroyko, Olga Zaborina, John C Alverdy
Signal exchange between intestinal epithelial cells, microbes and local immune cells is an important mechanism of intestinal homeostasis. Given that intestinal macrophages are in close proximity to both the intestinal epithelium and the microbiota, their pathologic interactions may result in epithelial damage. The present study demonstrates that co-incubation of murine macrophages with E. faecalis strains producing gelatinase (GelE) and serine protease (SprE) leads to resultant condition media (CM) capable of inducing reassembly of primary colonic epithelial cell monolayers...
2017: PloS One
https://www.readbyqxmd.com/read/28790180/pseudomonas-aeruginosa-lasb-protease-impairs-innate-immunity-in-mice-and-humans-by-targeting-a-lung-epithelial-cystic-fibrosis-transmembrane-regulator-il-6-antimicrobial-repair-pathway
#9
Vinciane Saint-Criq, Bérengère Villeret, Fabien Bastaert, Saadé Kheir, Aurélie Hatton, Aurélie Cazes, Zhou Xing, Isabelle Sermet-Gaudelus, Ignacio Garcia-Verdugo, Aleksander Edelman, Jean-Michel Sallenave
BACKGROUND: Pseudomonas aeruginosa lung infections are a huge problem in ventilator-associated pneumonia, cystic fibrosis (CF) and in chronic obstructive pulmonary disease (COPD) exacerbations. This bacterium secretes virulence factors that may subvert host innate immunity. OBJECTIVE: We evaluated the effect of P. aeruginosa elastase LasB, an important virulence factor secreted by the type II secretion system, on ion transport, innate immune responses and epithelial repair, both in vitro and in vivo...
August 8, 2017: Thorax
https://www.readbyqxmd.com/read/28789934/targeting-calpains-a-novel-immunomodulatory-approach-for-microbial-infections
#10
REVIEW
Vijay Kumar, Ahmad Ali
Calpains are a family of Ca(2+) dependent cytosolic non-lysosomal proteases with well conserved cysteine-rich domains for enzymatic activity. Due to their functional dependency on Ca(2+) concentrations, they are involved in various cellular processes that are regulated by intracellular ca(2+) concentration (i.e. embryo development, cell development and migration, maintenance of cellular architecture and structure etc.). Calpains are widely studied proteases in mammalian (i.e. mouse and human) physiology and pathophysiology due to their ubiquitous presence...
August 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28783135/enzymatic-and-pro-inflammatory-activities-of-bothrops-lanceolatus-venom-relevance-for-envenomation
#11
Marie Delafontaine, Isadora Maria Villas-Boas, Laurence Mathieu, Patrice Josset, Joël Blomet, Denise V Tambourgi
Bothrops lanceolatus, commonly named 'Fer-de-Lance', is an endemic snake of the French Caribbean Island of Martinique. Envenomations by B. lanceolatus present clinical aspects characterized by systemic thrombotic syndrome and important local inflammation, involving edema and pain but limited hemorrhage. To investigate mechanisms of venom-induced inflammation, B. lanceolatus venom was characterized, its cross-reactivity with bothropic antivenom explored, its cytotoxicity on human keratinocytes and vascular cells, and the production of cytokines and chemokines were analyzed...
August 7, 2017: Toxins
https://www.readbyqxmd.com/read/28776262/visceral-adipose-tissue-derived-serine-protease-inhibitor-prevents-the-development-of-monocrotaline-induced-pulmonary-arterial-hypertension-in-rats
#12
Yuzaburo Sakamoto, Satoshi Kameshima, Chiharu Kakuda, Yuta Okamura, Tomoko Kodama, Muneyoshi Okada, Hideyuki Yamawaki
Visceral adipose tissue-derived serine protease inhibitor (vaspin), a recently identified adipocytokine, inhibits inflammation, migration, and apoptosis of vascular cells. We have recently demonstrated that chronic administration of vaspin to spontaneously hypertensive rats partly prevents systemic hypertension through inhibiting inflammation and remodeling of vascular wall. Pulmonary arterial (PA) hypertension (PAH) is caused by PA remodeling, contractile dysfunction, and inflammatory responses. We tested the hypothesis that vaspin could prevent development of PAH in animal model...
August 3, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28775117/endotoxemia-shifts-neutrophils-with-timp-free-gelatinase-b-mmp-9-from-bone-marrow-to-periphery-and-induces-systematic-upregulation-of-timp-1
#13
Jennifer Vandooren, Wannes Swinnen, Estefania Ugarte-Berzal, Lise Boon, Daphne Dorst, Erik Martens, Ghislain Opdenakker
Lipopolysaccharides or endotoxins elicit an excessive host inflammatory response and lead to life-threatening conditions such as endotoxemia and septic shock. Lipopolysaccharides trigger mobilization and stimulation of leukocytes and exaggerated production of pro-inflammatory molecules including cytokines and proteolytic enzymes. Matrix metalloproteinase-9 (MMP-9) or gelatinase B, a protease stored in the tertiary granules of polymorphonuclear leukocytes, has been implicated in such inflammatory reactions. Moreover, several studies even pinpointed MMP-9 as a potential target molecule to counter excessive inflammation in endotoxemia...
August 3, 2017: Haematologica
https://www.readbyqxmd.com/read/28769800/cathepsin-s-is-involved-in-th17-differentiation-through-the-upregulation-of-il-6-by-activating-par-2-after-systemic-exposure-to-lipopolysaccharide-from-porphyromonas-gingivalis
#14
Masato Dekita, Zhou Wu, Junjun Ni, Xinwen Zhang, Yicong Liu, Xu Yan, Hiroshi Nakanishi, Ichiro Takahashi
Positive links have been found between periodontitis and numerous diseases in humans via persistent inflammation throughout the body. However, the main factors responsible for maintaining this pro-inflammatory condition are poorly understood. The spleen, the largest secondary immune organ, is a central hub regulating the immune response/inflammation due to the dendritic cell (DC) response to CD4(+) T cell subtype differentiation, and lysosomal proteinase cathepsin S (CatS) is known to be involved in DC functions...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28768771/activation-of-mas-related-g-protein-coupled-receptors-by-the-house-dust-mite-cysteine-protease-der-p1-provides-a-new-mechanism-linking-allergy-and-inflammation
#15
Vemuri B Reddy, Ethan A Lerner
Cysteine and serine proteases function via protease-activated (PARs) and mas-related G-protein coupled receptors (Mrgprs) to contribute to allergy and inflammation. Der p1 is a cysteine protease and major allergen from the house dust mite and is associated with allergic rhinitis and allergic asthma. Der p1 activates PAR2 and induces the release of the pro-inflammatory cytokine IL-6 from cells. However, the possibility that Der p1 acts on Mrgprs has not been considered. We report here that ratiometric calcium imaging reveals that Der p1 activates the human receptor MRGPRX1 and the mouse homolog MrgprC11, implicated previously in itch...
August 2, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28758900/tnf-is-required-for-tlr-ligand-mediated-but-not-protease-mediated-allergic-airway-inflammation
#16
Gregory S Whitehead, Seddon Y Thomas, Karim H Shalaby, Keiko Nakano, Timothy P Moran, James M Ward, Gordon P Flake, Hideki Nakano, Donald N Cook
Asthma is associated with exposure to a wide variety of allergens and adjuvants. The extent to which overlap exists between the cellular and molecular mechanisms triggered by these various agents is poorly understood, but it might explain the differential responsiveness of patients to specific therapies. In particular, it is unclear why some, but not all, patients benefit from blockade of TNF. Here, we characterized signaling pathways triggered by distinct types of adjuvants during allergic sensitization. Mice sensitized to an innocuous protein using TLR ligands or house dust extracts as adjuvants developed mixed eosinophilic and neutrophilic airway inflammation and airway hyperresponsiveness (AHR) following allergen challenge, whereas mice sensitized using proteases as adjuvants developed predominantly eosinophilic inflammation and AHR...
July 31, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28758717/epa%C3%A2-%C3%A2-dha-supplementation-reduces-pmn-activation-in-microenvironment-of-chronic-venous-leg-ulcers-a-randomized-double-blind-controlled-study
#17
Jodi C McDaniel, Laura Szalacha, Michelle Sales, Sashwati Roy, Scott Chafee, Narasimham Parinandi
Sustained high levels of activated polymorphonuclear leukocytes (PMNs) and PMN-derived proteases in the microenvironment of chronic venous leg ulcers (CVLUs) are linked to chronic inflammation and delayed healing. Uncontrolled PMN activity eventually destroys newly developed tissue and degrades critical growth factors. The bioactive components of fish oil (n-3 eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) have strong inflammation-resolving actions and have been shown to assuage PMN activity, but have not been tested in CVLU patients...
July 31, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28758430/calpain-inhibitor-attenuates-atherosclerosis-and-inflammation-in-atherosclerotic-rats-through-enos-no-nf-%C3%AE%C2%BAb-pathway
#18
Lan Yu, Meihui Yin, Xueyan Yang, Meili Lu, Futian Tang, Hongxin Wang
We previously reported that calpain, the Ca2+-sensitive cysteine protease, gets involved in the atherogenesis. This study was to investigate the effects of calpain inhibitor (CAI, 5 mg/kg/d) with or without NG-nitro-L-arginine-methyl ester (L-NAME) (100 mg/kg/d), the inhibitor of nitric oxide synthase (NOS), on atherosclerosis and inflammation in rat model induced by high cholesterol diet (HCD). The results demonstrated HCD increased protein expression of calpain-1 but not calpain-2 in aortic tissue. In addition, CAI reduced the thickness of atherosclerotic intima compared to HCD group, which was weakened by the L-NAME combination...
July 30, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28755289/downregulation-of-usp4-promotes-activation-of-microglia-and-subsequent-neuronal-inflammation-in-rat-spinal-cord-after-injury
#19
Xingjie Jiang, Mingchen Yu, Yiqing Ou, Yong Cao, Yu Yao, Ping Cai, Feng Zhang
NF-κB is involved in the activation of microglia, which induces secondary spinal cord injury (SCI). This process involves the activation of NF-κB signaling pathway by TRAF6 through its polyubiquitination function. We know that deubiquitination of TRAF6 mediated by deubiquitinating enzyme (DUB) significantly inhibits activation of NF-κB pathway. The ubiquitin-specific protease 4 (USP4) belongs to the deubiquitinase family. Therefore, we hypothesize that USP4 is involved in the microglial activation and subsequent neuronal inflammation after SCI...
July 28, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28751819/effects-of-secreted-mast-cell-mediators-on-retinal-pigment-epithelial-cells-focus-on-mast-cell-tryptase
#20
Rei Arai, Ayumi Usui-Ouchi, Yosuke Ito, Keitaro Mashimo, Akira Murakami, Nobuyuki Ebihara
Numerous mast cells are present in the choroid, but the effects of mast cell mediators on retinal pigment epithelial (RPE) cells are not well understood. We investigated the influence of mast cell mediators on RPE cells in vitro, focusing on tryptase. Expression of receptors was examined by the reverse transcription polymerase chain reaction. We also assessed production of interleukin 8 and vascular endothelial growth factor (VEGF) after RPE cells were stimulated with mast cell mediators by using an antibody array and enzyme-linked immunosorbent assay...
2017: Mediators of Inflammation
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