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Protease activated receptor 2

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https://www.readbyqxmd.com/read/28808141/a-critical-role-for-plasma-kallikrein-in-the-pathogenesis-of-autoantibody-induced-arthritis
#1
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/28797985/the-role-and-mechanism-of-cathepsin-g-in-dermatomyositis
#2
Siming Gao, Honglin Zhu, Huan Yang, Huali Zhang, Qiuxiang Li, Hui Luo
Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by CD4+ T cells and B cells infiltration in perivascular and muscle tissue. Although the infiltration of inflammatory cells plays a key role in muscle damage, the exact mechanism is not clear. Cathepsin G (CTSG) is a member of the serine proteases family and can increase the permeability of vascular endothelial cells and the chemotaxis of inflammatory cells. In this study, we found that the expression of CTSG was increased in peripheral blood mononuclear cells and muscle tissues of DM patients...
August 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28795730/role-of-garp-in-the-activation-of-latent-tgf-%C3%AE-1
#3
REVIEW
Julie Stockis, Olivier Dedobbeleer, Sophie Lucas
TGF-β1, 2 and 3 cytokines are involved in many cellular processes including cell proliferation, differentiation, migration and survival. Whereas TGF-β2 and 3 play important roles in embryonic development, TGF-β1 is mostly implicated in controlling immune responses after birth. The production of TGF-β1 is a tightly regulated process, occurring mostly at a post-translational level. Virtually all cells produce the latent, inactive form of TGF-β1. In latent TGF-β1, the mature TGF-β1 dimer is non-covalently associated to the Latency Associated Peptide, or LAP, which prevents binding to the TGF-β1 receptor...
August 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28769809/apixaban-enhances-vasodilatation-mediated-by-protease-activated-receptor-2-in-isolated-rat-arteries
#4
Ambra Villari, Giovanni Giurdanella, Claudio Bucolo, Filippo Drago, Salvatore Salomone
Apixaban (APX) is a direct inhibitor of factor X (FXa) approved for prophylaxis and treatment of deep venous thrombosis and atrial fibrillation. Because FXa activates protease-activated receptor 2 (PAR-2) in endothelium and vascular smooth muscle, inhibition of FXa by APX may affect vasomotor function. The effect of APX was assessed in vitro, by wire myography, in rat mesenteric resistance arteries (MRAs) and basilar arteries challenged with vasoconstrictors [phenylephrine (PE); 5-hydroxytryptamine (5-HT)], vasodilators [acetylcholine (ACh); sodium nitroprusside (SNP)] or with the PAR-2 peptide agonist SLIGRL...
2017: Frontiers in Pharmacology
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
#5
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/28759300/par-1-and-par-2-expression-is-enhanced-in-inflamed-odontoblast-cells
#6
M M P Alvarez, G E Moura, M F M Machado, G M Viana, C A de Souza Costa, L Tjäderhane, H B Nader, I L S Tersariol, F D Nascimento
Protease-activated receptors (PARs) are G protein-coupled receptors, which are activated by proteolytical cleavage of the amino-terminus and act as sensors for extracellular proteases. We hypothesized that PAR-1 and PAR-2 can be modulated by inflammatory stimulus in human dental pulp cells. PAR-1 and PAR-2 gene expression in human pulp tissue and MDPC-23 cells were analyzed by quantitative polymerase chain reaction. Monoclonal PAR-1 and PAR-2 antibodies were used to investigate the cellular expression of these receptors using Western blot, flow cytometry, and confocal microscopy in MDPC-23 cells...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28754863/pathological-expression-of-tissue-factor-confers-promising-antitumor-response-to-a-novel-therapeutic-antibody-sc1-in-triple-negative-breast-cancer-and-pancreatic-adenocarcinoma
#7
Xuesai Zhang, Qingrou Li, Hui Zhao, Lanping Ma, Tao Meng, Jianchang Qian, Rui Jin, Jingkang Shen, Ker Yu
The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF expression in TNBC clustered with higher levels of vimentin, basal-type keratins KRT5/14 and caveolin-1 but lower levels of luminal-type biomarkers. We developed a novel and specific anti-TF therapeutic antibody SC1, which displayed an exceedingly high potency against TF extracellular domain (EC50: 0...
July 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28751819/effects-of-secreted-mast-cell-mediators-on-retinal-pigment-epithelial-cells-focus-on-mast-cell-tryptase
#8
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
https://www.readbyqxmd.com/read/28724693/new-peptide-inhibitor-of-dipeptidyl-peptidase-iv-emdb-1-extends-the-half-life-of-glp-2-and-attenuates-colitis-in-mice-after-topical-administration
#9
Maciej Salaga, Anna Mokrowiecka, Marta Zielinska, Ewa Malecka-Panas, Radzislaw Kordek, Elzbieta Kamysz, Jakub Fichna
Protease inhibition has become a new possible approach in the inflammatory bowel disease (IBD) therapy. A serine exopeptidase, dipeptidyl peptidase IV (DPP IV) is responsible for inactivation of incretine hormone, glucagon-like peptide 2 (GLP-2), a potent stimulator of intestinal epithelium regeneration and growth. Recently we showed that the novel peptide analog of endomorphin-2, EMDB-1 is a potent blocker of DPP IV and has an inhibitory effect on gastrointestinal (GI) smooth muscle contractility. The aim of this study was to characterize the anti-inflammatory effect and mechanism of action of EMDB-1 in the mouse GI tract...
July 19, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28723894/cysteine-protease-cathepsin-b-mediates-radiation-induced-bystander-effects
#10
Yu Peng, Man Zhang, Lingjun Zheng, Qian Liang, Hanzeng Li, Jeng-Ting Chen, Hongyan Guo, Sawako Yoshina, Yu-Zen Chen, Xiang Zhao, Xiaoqi Wu, Bin Liu, Shohei Mitani, Jau-Song Yu, Ding Xue
The radiation-induced bystander effect (RIBE) refers to a unique process in which factors released by irradiated cells or tissues exert effects on other parts of the animal not exposed to radiation, causing genomic instability, stress responses and altered apoptosis or cell proliferation. Although RIBEs have important implications for radioprotection, radiation safety and radiotherapy, the molecular identities of RIBE factors and their mechanisms of action remain poorly understood. Here we use Caenorhabditis elegans as a model in which to study RIBEs, and identify the cysteine protease CPR-4, a homologue of human cathepsin B, as the first RIBE factor in nematodes, to our knowledge...
July 27, 2017: Nature
https://www.readbyqxmd.com/read/28718014/protein-hydrolysate-from-canned-sardine-and-brewing-by-products-improves-tnf-%C3%AE-induced-inflammation-in-an-intestinal-endothelial-co-culture-cell-model
#11
Elsa F Vieira, John Van Camp, Isabel M P L V O Ferreira, Charlotte Grootaert
PURPOSE: The anti-inflammatory activity of sardine protein hydrolysates (SPH) obtained by hydrolysis with proteases from brewing yeast surplus was ascertained. METHODS: For this purpose, a digested and desalted SPH fraction with molecular weight lower than 10 kDa was investigated using an endothelial cell line (EA.hy926) as such and in a co-culture model with an intestinal cell line (Caco-2). Effects of SPH <10 kDa on nitric oxide (NO) production, reactive oxygen species (ROS) inhibition and secretion of monocyte chemoattractant protein 1 (MCP-1), vascular endothelial growth factor (VEGF), chemokine IL-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) were evaluated in TNF-α-treated and untreated cells...
July 17, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28713240/the-coordinated-action-of-calcineurin-and-cathepsin-d-protects-against-%C3%AE-synuclein-toxicity
#12
Andreas Aufschnaiter, Lukas Habernig, Verena Kohler, Jutta Diessl, Didac Carmona-Gutierrez, Tobias Eisenberg, Walter Keller, Sabrina Büttner
The degeneration of dopaminergic neurons during Parkinson's disease (PD) is intimately linked to malfunction of α-synuclein (αSyn), the main component of the proteinaceous intracellular inclusions characteristic for this pathology. The cytotoxicity of αSyn has been attributed to disturbances in several biological processes conserved from yeast to humans, including Ca(2+) homeostasis, general lysosomal function and autophagy. However, the precise sequence of events that eventually results in cell death remains unclear...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28710422/enmd-1068-inhibits-liver-fibrosis-through-attenuation-of-tgf-%C3%AE-1-smad2-3-signaling-in-mice
#13
Quan Sun, Yan Wang, Jie Zhang, Jing Lu
Protease-activated receptor 2 (PAR-2) plays an important role in the pathogenesis of liver fibrosis. We studied the effect of N1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine (ENMD-1068), a PAR-2 antagonist, on the development of CCl4-induced liver fibrosis in mice and activation of hepatic stellate cells (HSCs) isolated from the mice. Before CCl4 injection, the mice were injected intraperitoneally with either 25 mg/kg or 50 mg/kg ENMD-1068 or with 200 μL of the vehicle control twice per week for 4 weeks...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709490/serum-levels-of-soluble-urokinase-plasminogen-activator-receptor-supar-as-a-marker-of-tuberculosis-treatment-efficacy
#14
V Indumati, V Vijay, D Krishnaswamy, V Rajeshwari, A Ramesh, D Shantala, A Shilpa
BACKGROUND: Upon diagnosis, Pulmonary Tuberculosis patients are treated for TB for a period of 6-9 months. At present, there exists very little indication of the efficacy of the particular treatment. A few previous studies have shown that soluble urokinase plasminogen activator receptor (SuPAR) may be used as treatment efficacy marker. SuPAR is a cellular receptor for serine protease urokinase plasminogen activator (uPA). Bacterial endotoxins and cytokines of the innate immune system stimulate the secretion of uPA in monocytes & neutrophils...
July 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28705940/characterisation-of-eppin-function-expression-and-activity-in-the-lung
#15
Aaron Scott, Arlene Glasgow, Donna Small, Simon Carlile, Maelíosa McCrudden, Denise McLean, Ryan Brown, Declan Doherty, Fionnuala T Lundy, Umar I Hamid, Cecilia M O'Kane, Daniel F McAuley, Malcolm Brodlie, Michael Tunney, J Stuart Elborn, Chris R Irwin, David J Timson, Clifford C Taggart, Sinéad Weldon
Eppin is a serine protease inhibitor expressed in male reproductive tissues.The aim of this study was to investigate the localisation and regulation of eppin expression in myeloid and epithelial cell lines, and explore its potential role as a multifunctional host defence protein.Using immunohistochemistry and Western blotting, eppin was detected in the lungs of patients with acute respiratory distress syndrome and cystic fibrosis lung disease. Expression of eppin in monocytic cells was unaffected by stimulation with Toll-like receptor agonists, cytokines and hormone receptor agonists...
July 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28705934/gq-pathway-regulates-proximal-c-type-lectin-like-receptor-2-clec-2-signaling-in-platelets
#16
Rachit Badolia, Vaishali Inamdar, Bhanu Kanth Manne, Carol Dangelmaier, Satya P Kunapuli
Platelets play a key role in the physiological hemostasis or pathological process of thrombosis. Rhodocytin, an agonist of the C-type lectin like receptor-2 (CLEC-2), elicits powerful platelet activation signals in conjunction with Src family kinases (SFKs), spleen tyrosine kinase (Syk), and phospholipase γ2 (PLCγ2). Previous reports have shown that rhodocytin-induced platelet aggregation depends on secondary mediators such as thromboxane (TxA2) and ADP, which are agonists for G protein coupled receptors (GPCRs) on platelets...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28705909/tgf-%C3%AE-inhibits-alveolar-protein-transport-by-promoting-shedding-regulated-intramembrane-proteolysis-and-transcriptional-downregulation-of-megalin
#17
Luciana C Mazzocchi, Christine U Vohwinkel, Konstantin Mayer, Susanne Herold, Rory E Morty, Werner Seeger, István Vadász
Disruption of the alveolar-capillary barrier is a hallmark of acute respiratory distress syndrome (ARDS) that leads to accumulation protein-rich edema in the alveolar space often resulting in comparable protein concentrations in alveolar edema and plasma and causing deleterious remodeling. Patients who survive ARDS have approximately three-times lower protein concentrations in the alveolar edema than non-survivors, thus, the ability to remove excess protein from the alveolar space may be critical for a positive outcome...
July 13, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28700339/trypsin-protease-activated-receptor-2-signaling-contributes-to-pancreatic-cancer-pain
#18
Jiao Zhu, Xue-Rong Miao, Kun-Ming Tao, Hai Zhu, Zhi-Yun Liu, Da-Wei Yu, Qian-Bo Chen, Hai-Bo Qiu, Zhi-Jie Lu
Pain treatment is a critical aspect of pancreatic cancer patient clinical care. This study investigated the role of trypsin-protease activated receptor-2 (PAR-2) in pancreatic cancer pain. Pancreatic tissue samples were collected from pancreatic cancer (n=22) and control patients (n=22). Immunofluorescence analyses confirmed colocalization of PAR-2 and neuronal markers in pancreatic cancer tissues. Trypsin levels and protease activities were higher in pancreatic cancer tissue specimens than in the controls...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28695794/the-natural-component-isolated-from-enterolobium-contortisiliquum-impairs-brain-tumors-and-affects-their-interactions-with-mesenchymal-stem-cells
#19
Camila Ramalho Bonturi, Helena Motaln, Mariana Cristina Cabral Silva, Bruno Ramos Salu, Marlon Vilela de Brito, Luciana de Andrade Luz Costa, Heron Fernandes Vieira Torquato, Natália Neto Dos Santos Nunes, Edgar Julian Paredes-Gamero, Tamara Lah Turnšek, Maria Luiza Vilela Oliva
Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with an overall patient survival of about 16 months. Thus, natural compounds with anti-cancer properties are gaining attention as possible alternatives for GBM treatment. Studies in various cancer models have shown the anti-cancer effects of the Enterolobium contortisiliquum Trypsin Inhibitor (EcTI). Here, we investigated the outcomes of EcTI on U87 cells, mesenchymal stem cells (MSC), and their direct cocultures (U87/MSC). MSC are present in tumor stroma and represent a potential drug delivery vehicle as the result of their tumor tropism...
July 11, 2017: Oncology Research
https://www.readbyqxmd.com/read/28695302/argatroban-attenuates-diabetic-cardiomyopathy-in-rats-by-reducing-fibrosis-inflammation-apoptosis-and-protease-activated-receptor-expression
#20
Yogesh Bulani, Shyam Sunder Sharma
PURPOSE: Chronic diabetes is associated with cardiovascular dysfunctions. Diabetic cardiomyopathy (DCM) is one of the serious cardiovascular complications associated with diabetes. Despite significant efforts in understanding the pathophysiology of DCM, management of DCM is not adequate due to its complex pathophysiology. Recently, involvement of protease-activated receptors (PARs) has been postulated in cardiovascular diseases. These receptors are activated by thrombin, trypsin, or other serine proteases...
July 10, 2017: Cardiovascular Drugs and Therapy
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