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Proteinase activated receptor

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https://www.readbyqxmd.com/read/28317204/cockroach-allergen-serine-proteinases-isolation-sequencing-and-signalling-via-proteinase-activated-receptor-2-par2
#1
Danny J Polley, Koichiro Mihara, Rithwik Ramachandran, Harissios Vliagoftis, Bernard Renaux, Mahmoud Saifeddine, Michael O Daines, Scott Boitano, Morley D Hollenberg
BACKGROUND: Allergy to the German cockroach (Blattella germanica) is a significant asthma risk factor for inner-city communities. Cockroach, like other allergens, contains trypsin-like enzyme activity that contributes to allergenicity and airway inflammation by activating proteinase-activated receptors (PARs). To date, the enzymes responsible for the proteolytic activity of German cockroach allergen have not been characterized. OBJECTIVES: We aimed to identify, isolate and characterize the trypsin-like proteinases in German cockroach allergen extracts used for clinical skin tests...
March 20, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28299632/transgenic-expression-of-a-canonical-wnt-inhibitor-kallistatin-is-associated-with-decreased-circulating-cd19-b-lymphocytes-in-the-peripheral-blood
#2
Jeffrey D McBride, Xiaochen Liu, William L Berry, Ralf Janknecht, Rui Cheng, Kelu Zhou, Evangelos V Badiavas, Jian-Xing Ma
Members of the family of serine proteinase inhibitors, such as kallistatin, have been shown to inhibit canonical Wnt-TCF/LEF-β-catenin signaling via their interactions with the Wnt co-receptor LRP6. Yet the effects of transgenic overexpression of anti-Wnt serpins on hematopoiesis and lymphopoiesis are not well known. We studied the effects of human kallistatin (SERPINA4) on Wnt reporter activity in various cell types throughout the hematopoietic system and associated impacts on circulating white blood cell profiles...
March 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28268238/role-of-chemically-modified-tetracyclines-in-the-management-of-periodontal-diseases-a-review
#3
Archit A Ghangurde, Kiran Kumar Ganji, Manohar L Bhongade, Bhumika Sehdev
Researchers have found that Chemically Modified Tetracyclines (CMTs) act through multiple mechanisms, affecting several parameters of osteoclast function and consequently inhibit bone resorption by altering intracellular calcium concentration and interacting with the putative calcium receptor; decreasing ruffled border area; diminishing acid production; diminishing the secretion of lysosomal cysteine proteinases (cathepsins); inducing cell retraction by affecting podosomes; inhibiting osteoclast gelatinase activity; selectively inhibiting osteoclast ontogeny or development; and inducing apoptosis or programmed cell death of osteoclasts...
March 7, 2017: Drug Research
https://www.readbyqxmd.com/read/28216875/antidermatophytic-and-protease-inhibiting-activities-of-zerumbone-a-natural-sesquiterpene-from-the-rhizome-of-zingiber-zerumbet-l-roscoe-ex-j-e-smith
#4
Madhavankutty Jyothilakshmi, Mathew Jyothis, Gokulanathan Nair Hari Narayanan, Mukalel Sankunni Latha
CONTEXT: Due to increase in the number of patients with impaired immunity, incidence of dermatophytoses has increased considerably. Antidermatophytic agents with anti-inflammatory and protease-inhibiting activities will help in restricting inflammatory response associated with dermatophytoses. AIMS: The present study aims to evaluate antidermatophytic and protease-inhibiting activities of zerumbone. Cytotoxicity was tested using Chang liver cell line as a preliminary step in toxicity study...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28216055/human-eosinophils-constitutively-express-a-unique-serine-protease-prss33
#5
Sumika Toyama, Naoko Okada, Akio Matsuda, Hideaki Morita, Hirohisa Saito, Takao Fujisawa, Susumu Nakae, Hajime Karasuyama, Kenji Matsumoto
BACKGROUND: Eosinophils play important roles in asthma, especially airway remodeling, by producing various granule proteins, chemical mediators, cytokines, chemokines and proteases. However, protease production by eosinophils is not fully understood. In the present study, we investigated the production of eosinophil-specific proteases/proteinases by transcriptome analysis. METHODS: Human eosinophils and other cells were purified from peripheral blood by density gradient sedimentation and negative/positive selections using immunomagnetic beads...
February 16, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28212842/pathophysiological-consequences-of-receptor-mistraffic-tales-from-the-platelet-p2y12-receptor
#6
Margaret R Cunningham, Riyaad Aungraheeta, Stuart J Mundell
Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function...
February 14, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28196851/inhibition-of-lipopolysaccharide-induced-osteoclast-formation-and-bone-resorption-in-vitro-and-in-vivo-by-cysteine-proteinase-inhibitors
#7
Fredrik Strålberg, Ali Kassem, Franciszek Kasprzykowski, Magnus Abrahamson, Anders Grubb, Catharina Lindholm, Ulf H Lerner
Inflammation-induced bone destruction is a major treatment target in many inflammatory skeletal diseases. The aim of this study was to investigate if the cysteine proteinase inhibitors cystatin C, fungal cysteine proteinase inhibitor (E-64), and N-benzyloxycarbonyl-arginyl-leucyl-valyl-glycyl-diazomethane acetate (Z-RLVG-CHN2) can inhibit LPS-induced osteoclast formation. Mouse bone marrow macrophages (BMMs) were isolated and primed with receptor activator of NF-κB ligand (RANKL) for 24 h, followed by stimulation with LPS, with and without inhibitors...
February 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28191683/immediate-type-allergic-and-protease-mediated-reactions-are-involved-in-scratching-behavior-induced-by-topical-application-of-dermatophagoides-farinae-extract-in-nc-nga-mice
#8
Yoshihito Yamada, Yuhki Ueda, Aki Nakamura, Shoji Kanayama, Rie Tamura, Kei Hashimoto, Tatsumi Matsumoto, Ritsuko Ishii
Atopic dermatitis (AD)-like dermatitis can be induced by repeated topical application of an ointment containing Dermatophagoides farinae body (Dfb) extract in NC/Nga mice. This AD-like murine model also exhibits a biphasic increase in the number of scratching behavior after topical application of Dfb ointment. In this study, we investigated the possible mechanisms underlying the scratching behavior in each phase. An increase in the content of mast cell derived mediators such as histamine and 5-hydroxytryptamine in the lesional skin and increased vascular permeability were observed in the early phase after the Dfb ointment application...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28179424/altered-methylation-of-specific-dna-loci-in-the-liver-of-bhmt-null-mice-results-in-repression-of-iqgap2-and-f2rl2-and-is-associated-with-development-of-preneoplastic-foci
#9
Daniel S Lupu, Luz D Orozco, Ying Wang, John M Cullen, Matteo Pellegrini, Steven H Zeisel
Folate B12-dependent remethylation of homocysteine is important, but less is understood about the importance of the alternative betaine-dependent methylation pathway-catalyzed by betaine-homocysteine methyltransferase (BHMT)-for establishing and maintaining adequate DNA methylation across the genome. We studied C57Bl/6J Bhmt (betaine-homocysteine methyltransferase)-null mice at age 4, 12, 24, and 52 wk (N = 8) and observed elevation of S-adenosylhomocysteine concentrations and development of preneoplastic foci in the liver (increased placental glutathione S-transferase and cytokeratin 8-18 activity; starting at 12 wk)...
February 8, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28138552/anti-myeloperoxidase-antibodies-attenuate-the-monocyte-response-to-lps-and-shape-macrophage-development
#10
Reena J Popat, Seran Hakki, Alpesh Thakker, Alice M Coughlan, Julie Watson, Mark A Little, Corinne M Spickett, Paul Lavender, Behdad Afzali, Claudia Kemper, Michael G Robson
Anti-neutrophil cytoplasmic antibody (ANCA) vasculitis is characterized by the presence of autoantibodies to myeloperoxidase and proteinase-3, which bind monocytes in addition to neutrophils. While a pathological effect on neutrophils is acknowledged, the impact of ANCA on monocyte function is less well understood. Using IgG from patients we investigated the effect of these autoantibodies on monocytes and found that anti-myeloperoxidase antibodies (MPO-ANCA) reduced both IL-10 and IL-6 secretion in response to LPS...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28126849/targeting-a-proteinase-activated-receptor-4-par4-carboxyl-terminal-motif-to-regulate-platelet-function
#11
Rithwik Ramachandran, Koichiro Mihara, Pierre Thibeault, Christina M Vanderboor, Björn Petri, Mahmoud Saifeddine, Michel Bouvier, Morley D Hollenberg
Thrombin initiates human platelet aggregation by coordinately activating proteinase-activated receptors (PARs) 1 and 4. However, targeting PAR1 with an orthosteric-tethered ligand binding-site antagonist results in bleeding, possibly owing to the important role of PAR1 activation on cells other than platelets. Because of its more restricted tissue expression profile, we have therefore turned to PAR4 as an antiplatelet target. We have identified an intracellular PAR4 C-terminal motif that regulates calcium signaling and β-arrestin interactions...
April 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28116092/teleocidin-a2-inhibits-human-proteinase-activated-receptor-2-signaling-in-tumor-cells
#12
Sonja Stahn, Lisa Thelen, Ina-Maria Albrecht, Jens Bitzer, Thomas Henkel, Nicole Elisabeth Teusch
Enhanced expression of the proteinase-activated receptor 2 (PAR2) is linked to cell proliferation and migration in many cancer cell types. The role of PAR2 in cancer progression strongly illustrates the need for PAR2-inhibiting compounds. However, to date, potent and selective PAR2 antagonists have not been reported. The natural product teleocidin A2 was characterized against PAR2-activating peptide SLIGKV-NH 2, and trypsin-induced PAR2-dependent intracellular Ca(2+) mobilization in tumor and in primary endothelial or epithelial cells...
August 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28110689/cannabinoids-possible-agents-for-treatment-of-psoriasis-via-suppression-of-angiogenesis-and-inflammation
#13
Amir Hossein Norooznezhad, Fatemeh Norooznezhad
Psoriasis is a chronic skin disease also affecting other sites such as joints. This disease highly depends on inflammation and angiogenesis as well as other pathways. At each step of the psoriasis molecular pathway, different inflammatory cytokines and angiogenic growth factors are involved such as hypoxia inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), matrix metalo proteinases (MMPs), basic fibroblast growth factor (bFGF), Angiopoitin-2, interleukin-8 (IL-8), IL-17, and IL-2. Beside the mentioned growth factors and cytokines, cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which play roles in both angiogenesis and inflammation are also involved in the pathogenesis...
February 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28088386/trypsin-induces-biphasic-muscle-contraction-and-relaxation-via-transient-receptor-potential-vanilloid-1-and-neurokinin-receptors-1-2-in-porcine-esophageal-body
#14
Bai Xiaopeng, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Kayoko Nakano, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura
Duodenal reflux of fluids containing trypsin relates to refractory gastroesophageal reflux disease (GERD). Esophageal peristalsis and clearance are important factors in GERD pathogenesis. However, the function of trypsin in esophageal body contractility is not fully understood. In this study, effects of trypsin on circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the porcine esophageal body were examined. Trypsin elicited a concentration dependent biphasic response, a major contraction and a subsequent relaxation only in CSM...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27995765/shockwaves-prevent-from-heart-failure-after-acute-myocardial-ischaemia-via-rna-protein-complexes
#15
Can Tepeköylü, Uwe Primessnig, Leo Pölzl, Michael Graber, Daniela Lobenwein, Felix Nägele, Elke Kirchmair, Elisabeth Pechriggl, Michael Grimm, Johannes Holfeld
Shock wave treatment (SWT) was shown to induce regeneration of ischaemic myocardium via Toll-like receptor 3 (TLR3). The antimicrobial peptide LL37 gets released by mechanical stress and is known to form complexes with nucleic acids thus activating Toll-like receptors. We suggested that SWT in the acute setting prevents from the development of heart failure via RNA/protein release. Myocardial infarction in mice was induced followed by subsequent SWT. Heart function was assessed 4 weeks later via transthoracic echocardiography and pressure-volume measurements...
April 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27993717/mapping-transmembrane-residues-of-proteinase-activated-receptor-2-par2-that-influence-ligand-modulated-calcium-signaling
#16
J Y Suen, M N Adams, J Lim, P K Madala, W Xu, A J Cotterell, Y He, M K Yau, J D Hooper, D P Fairlie
Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor involved in metabolism, inflammation, and cancers. It is activated by proteolysis, which exposes a nascent N-terminal sequence that becomes a tethered agonist. Short synthetic peptides corresponding to this sequence also activate PAR2, while small organic molecules show promising PAR2 antagonism. Developing PAR2 ligands into pharmaceuticals is hindered by a lack of knowledge of how synthetic ligands interact with and differentially modulate PAR2...
December 16, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27986809/urokinase-type-plasminogen-activator-upa-binding-to-the-upa-receptor-upar-promotes-axonal-regeneration-in-the-central-nervous-system
#17
Paola Merino, Ariel Diaz, Valerie Jeanneret, Fang Wu, Enrique Torre, Lihong Cheng, Manuel Yepes
Axonal injury is a common cause of neurological dysfunction. Unfortunately, in contrast to axons from the peripheral nervous system, the limited capacity of regeneration of central nervous system (CNS) axons is a major obstacle for functional recovery in patients suffering neurological diseases that involve the subcortical white matter. Urokinase-type plasminogen activator (uPA) is a serine proteinase that upon binding to the urokinase-type plasminogen activator receptor (uPAR) catalyzes the conversion of plasminogen into plasmin on the cell surface...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27931798/differential-expression-of-low-density-lipoprotein-receptor-related-protein-1-lrp-1-and-matrix-metalloproteinase-9-mmp-9-in-prostate-gland-from-normal-to-malignant-lesions
#18
Mónica B Gilardoni, María M Remedi, Mabel Oviedo, Tristán Dellavedova, Juan P Sarría, Laura Racca, Mariana Dominguez, Claudia G Pellizas, Ana C Donadio
BACKGROUND: Metalloproteinases (MMPs) are relevant modulators of inflammation, tumor microenvironment, cancer invasion and metastasis. They can be regulated by the Low density lipoprotein Receptor-related Protein 1 (LRP-1), a receptor reported to mediate the clearance of lipoproteins, extracellular matrix (ECM) macromolecules and proteinases. The aim of this study was to evaluate the expression of LRP-1, MMP-2 and MMP-9 across various grades of prostatic diseases as benign prostatic hyperplasia (BPH), BPH plus prostatitis (BPH+P), high grade prostatic intraepithelial neoplasia (HGPIN) and prostate cancer (PCa)...
January 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27917624/relationships-between-high-mobility-group-protein-b1-and-triggering-receptor-expressed-on-myeloid-cells-concentrations-in-gingival-crevicular-fluid-and-chronic-periodontitis
#19
Mojgan Paknejad, Mandana Sattari, Zohreh Roozbahani, Morteza Ershadi, Ali Mehrfard
One of the inflammatory mediators which is secreted by inflammatory cells is high-mobility group protein B1 (HMGB1). Interaction of HMGB1 and toll-like receptors (TLRs) leads to increased production of inflammatory cytokines. On the other hand, it was shown that triggering receptor expressed on myeloid cells (TREM-1) also can be activated by TLRs, and its soluble form (sTREM-1) can be formed by cleaving of membrane-bound form of TREM-1 proteinases. Since there is not enough knowledge about the precise role of HMGB1 and sTREM-1 in periodontal diseases, the aim of this study was to evaluate the concentration of HMGB1 and sTREM-1 in gingival crevicular fluid (GCF) samples of patients with chronic periodontitis...
October 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27916875/proteinase-activated-receptor-2-is-a-novel-regulator-of-tgf-%C3%AE-signaling-in-pancreatic-cancer
#20
REVIEW
David Witte, Franziska Zeeh, Thomas Gädeken, Frank Gieseler, Bernhard H Rauch, Utz Settmacher, Roland Kaufmann, Hendrik Lehnert, Hendrik Ungefroren
TGF-β has a dual role in tumorigenesis, acting as a tumor suppressor in normal cells and in the early stages of tumor development while promoting carcinogenesis and metastasis in advanced tumor stages. The final outcome of the TGF-β response is determined by cell-autonomous mechanisms and genetic alterations such as genomic instability and somatic mutations, but also by a plethora of external signals derived from the tumor microenvironment, such as cell-to-cell interactions, growth factors and extracellular matrix proteins and proteolytic enzymes...
November 30, 2016: Journal of Clinical Medicine
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