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https://www.readbyqxmd.com/read/28921694/protease-activated-receptor-2-controls-myelin-development-resiliency-and-repair
#1
Hyesook Yoon, Maja Radulovic, Grant Walters, Alex R Paulsen, Kristen Drucker, Phillip Starski, Jianmin Wu, David P Fairlie, Isobel A Scarisbrick
Oligodendrocytes are essential regulators of axonal energy homeostasis and electrical conduction and emerging target cells for restoration of neurological function. Here we investigate the role of protease activated receptor 2 (PAR2), a unique protease activated G protein-coupled receptor, in myelin development and repair using the spinal cord as a model. Results demonstrate that genetic deletion of PAR2 accelerates myelin production, including higher proteolipid protein (PLP) levels in the spinal cord at birth and higher levels of myelin basic protein and thickened myelin sheaths in adulthood...
September 18, 2017: Glia
https://www.readbyqxmd.com/read/28881035/protease-activated-receptor-2-contributes-to-toxoplasma-gondii-mediated-gut-inflammation
#2
Chrystelle Bonnart, Guylène Feuillet, Virginie Vasseur, Nicolas Cenac, Nathalie Vergnolle, Nicolas Blanchard
Toxoplasma gondii is a widespread intracellular parasite, which naturally enters the organism via the oral route and cross the intestinal barrier to disseminate. In addition to neuronal and ocular pathologies, this pathogen also causes gut inflammation in a number of animals. This infection-triggered inflammation has been extensively studied in the C57BL/6 mice, highlighting the importance of the immune cells and their mediators in the development of gut pathology. However, despite their importance in inflammation, the role of Protease-Activated Receptors (PAR) was never reported in the context of T...
September 7, 2017: Parasite Immunology
https://www.readbyqxmd.com/read/28842394/tgf-%C3%AE-1-alk5-mediated-cell-migration-is-dependent-on-the-protein-par2-but-not-on-par2-stimulated-gq-calcium-signaling
#3
Hendrik Ungefroren, David Witte, Koichiro Mihara, Bernhard H Rauch, Petra Henklein, Olaf Johren, Shirin Bonni, Utz Settmacher, Hendrik Lehnert, Morley D Hollenberg, Roland Kaufmann, Frank Gieseler
Transforming growth factor-β (TGF-β), serine proteinases such as trypsin, and proteinase-activated receptor 2 (PAR2) promote tumor development by stimulating invasion and metastasis. Previously, we found that in cancer cells derived from pancreatic ductal adenocarcinoma (PDAC) PAR2 protein is necessary for TGF-β1-dependent cell motility (Zeeh et al., 2016). Here, we show in the same cells that, conversely, the type I TGF-β; receptor ALK5 is dispensable for trypsin and PAR2 activating peptide (PAR2-AP)-induced migration...
August 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28835277/prophylactic-inhibition-of-neutrophil-elastase-prevents-the-development-of-chronic-neuropathic-pain-in-osteoarthritic-mice
#4
Milind M Muley, Eugene Krustev, Allison R Reid, Jason J McDougall
BACKGROUND: A subset of osteoarthritis (OA) patients experience joint pain with neuropathic characteristics. Mediators such as neutrophil elastase, a serine proteinase, may be released during acute OA inflammatory flares. We have previously shown that local administration of neutrophil elastase causes joint inflammation and pain via activation of proteinase-activated receptor-2 (PAR2). The aim of this study was to examine the contribution of endogenous neutrophil elastase and PAR2 to the development of joint inflammation, pain, and neuropathy associated with monoiodoacetate (MIA)-induced experimental OA...
August 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28827518/activated-protein-c-protects-from-gvhd-via-par2-par3-signalling-in-regulatory-t-cells
#5
Satish Ranjan, Alexander Goihl, Shrey Kohli, Ihsan Gadi, Mandy Pierau, Khurrum Shahzad, Dheerendra Gupta, Fabian Bock, Hongjie Wang, Haroon Shaikh, Thilo Kähne, Dirk Reinhold, Ute Bank, Ana C Zenclussen, Jana Niemz, Tina M Schnöder, Monika Brunner-Weinzierl, Thomas Fischer, Thomas Kalinski, Burkhart Schraven, Thomas Luft, Jochen Huehn, Michael Naumann, Florian H Heidel, Berend Isermann
Graft-vs.-host disease (GvHD) is a major complication of allogenic hematopoietic stem-cell(HSC) transplantation. GvHD is associated with loss of endothelial thrombomodulin, but the relevance of this for the adaptive immune response to transplanted HSCs remains unknown. Here we show that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates GvHD aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on regulatory T-cells (Tregs, CD4(+)FOXP3(+))...
August 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28797985/the-role-and-mechanism-of-cathepsin-g-in-dermatomyositis
#6
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...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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
#7
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
#8
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/28754863/pathological-expression-of-tissue-factor-confers-promising-antitumor-response-to-a-novel-therapeutic-antibody-sc1-in-triple-negative-breast-cancer-and-pancreatic-adenocarcinoma
#9
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/28754162/sensitization-of-asic3-by-proteinase-activated-receptor-2-signaling-contributes-to-acidosis-induced-nociception
#10
Jing Wu, Ting-Ting Liu, Yi-Mei Zhou, Chun-Yu Qiu, Ping Ren, Ming Jiao, Wang-Ping Hu
BACKGROUND: Tissue acidosis and inflammatory mediators play critical roles in pain. Pro-inflammatory agents trypsin and tryptase cleave and activate proteinase-activated receptor 2 (PAR2) expressed on sensory nerves, which is involved in peripheral mechanisms of inflammation and pain. Extracellular acidosis activates acid-sensing ion channel 3 (ASIC3) to trigger pain sensation. Here, we show that a functional interaction of PAR2 and ASIC3 could contribute to acidosis-induced nociception...
July 28, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28751819/effects-of-secreted-mast-cell-mediators-on-retinal-pigment-epithelial-cells-focus-on-mast-cell-tryptase
#11
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/28694438/stress-induces-more-serious-barrier-dysfunction-in-follicle-associated-epithelium-than-villus-epithelium-involving-mast-cells-and-protease-activated-receptor-2
#12
Lei Zhang, Jun Song, Tao Bai, Wei Qian, Xiao-Hua Hou
Psychological stress has been associated with intestinal epithelial hyperpermeability, the basic process in various functional and organic bowel diseases. In the present study, we aimed to clarify the differences and underlining mechanisms in stress-induced barrier disruption in functionally and structurally distinct epitheliums, including the villus epithelium (VE) and follicle-associated epithelium (FAE), a specialized epithelium overlaid the domes of Peyer's lymphoid follicles. Employing an Ussing Chamber system, the epithelial permeability was assessed in rats following water avoidance stress (WAS) in vivo and in mucosa tissues exposed to corticotropin-releasing factor (CRF) ex vivo...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694352/protease-activated-receptor-2-promotes-kidney-tubular-epithelial-inflammation-by-inhibiting-autophagy-via-the-pi3k-akt-mtor-signalling-pathway
#13
Chunyang Du, Tao Zhang, Xia Xiao, Yonghong Shi, Huijun Duan, Yunzhuo Ren
Protease-activated receptor-2 (PAR2), which belongs to a specific class of the G-protein-coupled receptors, is central to several inflammation processes. However, the precise molecular mechanism involved remains undefined. Autophagy has been previously shown to affect inflammation. In the present study, we examine the effect of PAR2 on kidney tubular epithelial autophagy and on autophagy-related inflammation and reveal the underlying mechanism involved. Autophagic activity and levels of autophagic marker LC3 were examined in human kidney tubular epithelial cells with PAR2 knockdown or overexpression...
August 2, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28643288/inhibitory-effect-of-fsllry-nh2-on-inflammatory-responses-induced-by-hydrogen-peroxide-in-hepg2-cells
#14
Yeon Joo Lee, Su Jin Kim, Kyoung Wan Kwon, Won Mo Lee, Wi Joon Im, Uy Dong Sohn
Proteinase activated receptor 2 (PAR2), which is localized in the GI tract, the respiratory system, and the kidney tubules is a G protein-coupled receptor associated with inflammation, metabolism, and disease. The aim of this study was to explore the role of PAR2 in hydrogen peroxide (H2O2)-induced HepG2 cells by using FSLLRY-NH2 a PAR2 antagonist. H2O2 treatment resulted in induction of PAR2 in esophageal, gastric, and liver cells, with the most robust response being in HepG2 cells. Furthermore, this effect was dose-dependent in HepG2 cells...
June 22, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28614190/nonhistaminergic-and-mechanical-itch-sensitization-in-atopic-dermatitis
#15
H H Andersen, J Elberling, H Sølvsten, G Yosipovitch, L Arendt-Nielsen
Chronic or episodic severe itch is recurrent in atopic dermatitis (AD). Nonhistaminergic itch pathways are suggested to dominate in AD itch, contributing to an "itch-scratch-itch cycle" that prolongs and worsens itch, pain, and skin lesions. We hypothesized that nonhistaminergic neuronal sensitization contributes to itch in AD. Hence, we compared sensitivity with thermal, mechanical, and chemical pruritic stimuli in patients with AD and controls. The study comprised 25 patients with AD with chronic itch and 25 healthy controls...
September 2017: Pain
https://www.readbyqxmd.com/read/28613153/precision-in-the-design-of-an-experimental-study-deflects-the-significance-of-proteinase-activated-receptor-2-expression-in-scrapie-inoculated-mice
#16
Zdenka Hanusova, Tibor Mosko, Radoslav Matej, Karel Holada
Proteinase-activated receptor 2 (PAR2) is suspected to modulate the pathogenesis of various neurodegenerative conditions. We previously described delayed onset of clinical symptoms and prolonged survival of PAR2-deficient mice after intracerebral inoculation with prions. Here we report the results from a refined blinded study that aimed to investigate the effects of PAR2 deletion on scrapie pathogenesis after peripheral infection. This study failed to confirm that PAR2 deficiency impacts on the length of the incubation period, with PAR2-/- and PAR2+/+ littermates developing scrapie at the same time...
June 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28522609/coagulation-factor-viia-mediated-protease-activated-receptor-2-activation-leads-to-%C3%AE-catenin-accumulation-via-the-akt-gsk3%C3%AE-pathway-and-contributes-to-breast-cancer-progression
#17
Abhishek Roy, Shabbir A Ansari, Kaushik Das, Ramesh Prasad, Anindita Bhattacharya, Suman Mallik, Ashis Mukherjee, Prosenjit Sen
Cell migration and invasion are very characteristic features of cancer cells that promote metastasis, which is one of the most common causes of mortality among cancer patients. Emerging evidence has shown that coagulation factors can directly mediate cancer-associated complications either by enhancing thrombus formation or by initiating various signaling events leading to metastatic cancer progression. It is well established that, apart from its distinct role in blood coagulation, coagulation factor FVIIa enhances aggressive behaviors of breast cancer cells, but the underlying signaling mechanisms still remain elusive...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28503577/the-role-of-proteinase-activated-receptors-1-and-2-in-the-regulation-of-periodontal-tissue-metabolism-and-disease
#18
REVIEW
E S Rovai, M Holzhausen
Proteinase-activated receptors 1 (PAR1) and 2 (PAR2) are the most highly expressed members of the PAR family in the periodontium. These receptors regulate periodontal inflammatory and repair processes through their activation by endogenous and bacterial enzymes. PAR1 is expressed by the periodontal cells such as human gingival fibroblasts, gingival epithelial cells, periodontal ligament cells, osteoblasts, and monocytic cells and can be activated by thrombin, matrix metalloproteinase 1 (MMP-1), MMP-13, fibrin, and gingipains from Porphyromonas gingivalis...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28485540/proteinase-activated-receptor-2-modulates-ve-cadherin-expression-to-affect-human-vascular-endothelial-barrier-function
#19
Rui Zhang, Jianjun Ge
Published data indicate that the protease-activated receptor (PAR) 2 is involved in the pathogenesis of some cardiovascular diseases; the underlying mechanism is to be further investigated. Ve-cadherin is a critical molecule in maintaining the endothelial barrier integrity. This study aims to investigate the role of PAR2 activation in compromising the cardiac endothelial barrier function. In this study, human umbilical vein endothelial cells (Huvec cells) were cultured into monolayers using as an in vitro model of barrier function...
May 9, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28483635/crystal-structure-of-tissue-factor-in-complex-with-antibody-10h10-reveals-the-signaling-epitope
#20
Alexey Teplyakov, Galina Obmolova, Thomas J Malia, Bingyuan Wu, Yonghong Zhao, Susann Taudte, G Mark Anderson, Gary L Gilliland
Tissue factor (TF) initiates the extrinsic pathway of blood coagulation through sequential binding and activation of coagulation factors VII (FVII) and X (FX). In addition, through activation of G-protein-coupled protease activated receptors (PARs) TF induces cell signaling that is related to cancer, angiogenesis and inflammation. Monoclonal antibodies (mAbs) proved to be a useful tool for studying the interplay between TF signaling and coagulation. MAb 10H10 is unique in that it blocks the signaling pathway and thus inhibits angiogenesis and tumor growth without interfering with coagulation...
May 5, 2017: Cellular Signalling
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