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https://www.readbyqxmd.com/read/29778505/novel-peptide-nanoparticle-biased-antagonist-of-ccr3-blocks-eosinophil-recruitment-and-airway-hyperresponsiveness
#1
Milica Grozdanovic, Kimberly G Laffey, Hazem Abdelkarim, Ben Hitchinson, Anantha Harijith, Hyung-Geon Moon, Gye Young Park, Lee K Rousslang, Joanne C Masterson, Glenn T Furuta, Nadya I Tarasova, Vadim Gaponenko, Steven J Ackerman
BACKGROUND: Chemokine signaling through CCR3 is a key regulatory pathway for eosinophil recruitment into tissues associated with allergic inflammation and asthma. To date, none of the CCR3 antagonists have shown efficacy in clinical trials. One reason may be their unbiased mode of inhibition that prevents receptor internalization, leading to drug tolerance. OBJECTIVE: We sought to develop a novel peptide nanoparticle CCR3 inhibitor (R321) with a biased mode of inhibition that would block G-protein signaling, but enable or promote receptor internalization...
May 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29776427/rheumatoid-meningitis-developed-in-patient-with-stable-rheumatoid-arthritis-and-myasthenia-gravis-detailed-analysis-of-intracranial-inflammation-using-flow-cytometry
#2
Miki Oono, Yoshimasa Fujita, Nobuaki Uchida, Ukichiro Kawai, Michiyo Fujita-Nakata, Megumi Nakanishi, Mitsuru Sanada, Shigemi Nagayama, Makoto Matsui
BACKGROUND: Rheumatoid meningitis (RM) is a rare disorder that often develops during a remission phase of rheumatoid arthritis (RA). This is the first study to demonstrate differences in regard to immunological disturbance between blood and cerebrospinal fluid (CSF) samples obtained from a patient with RM using flow cytometry. CASE PRESENTATION: A 36-year-old woman with RA and generalized myasthenia gravis (MG) developed RM during a remission phase. Although both RA and MG were stable and well controlled, she noticed fever, headache, and transient sensory disturbance...
May 18, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29772059/the-orphan-g-protein-coupled-receptor-75-signaling-is-activated-by-the-chemokine-ccl5
#3
Simona Dedoni, Lee A Campbell, Brandon K Harvey, Valeria Avdoshina, Italo Mocchetti
The chemokine CCL5 prevents neuronal cell death mediated both by amyloid β, as well as the human immunodeficiency virus (HIV) viral proteins gp120 and Tat. Because CCL5 binds to CCR5, CCR3 and/or CCR1 receptors, it is unclear which of these receptors plays a role in neuroprotection. Indeed, CCL5 also has neuroprotective activity in cells lacking these receptors. CCL5 may bind to a G protein-coupled receptor 75 (GPR75), which encodes for a 540 amino-acid orphan receptor of the Gqα family. In this study, we have used SH-SY5Y human neuroblastoma cells to characterize whether CCL5 could activate a Gq signaling through GPR75...
May 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29740512/bioinformatic-analysis-and-identification-of-potential-prognostic-micrornas-and-mrnas-in-thyroid-cancer
#4
Jianing Tang, Deguang Kong, Qiuxia Cui, Kun Wang, Dan Zhang, Qianqian Yuan, Xing Liao, Yan Gong, Gaosong Wu
Thyroid cancer is one of the most common endocrine malignancies. Multiple evidences revealed that a large number of microRNAs and mRNAs were abnormally expressed in thyroid cancer tissues. These microRNAs and mRNAs play important roles in tumorigenesis. In the present study, we identified 72 microRNAs and 1,766 mRNAs differentially expressed between thyroid cancer tissues and normal thyroid tissues and evaluated their prognostic values using Kaplan-Meier survival curves by log-rank test. Seven microRNAs (miR-146b, miR-184, miR-767, miR-6730, miR-6860, miR-196a-2 and miR-509-3) were associated with the overall survival...
2018: PeerJ
https://www.readbyqxmd.com/read/29726281/exopolysaccharide-from-bifidobacterium-longum-subsp-longum-35624%C3%A2-modulates-murine-allergic-airway-responses
#5
E Schiavi, S Plattner, N Rodriguez-Perez, W Barcik, R Frei, R Ferstl, M Kurnik-Lucka, D Groeger, R Grant, J Roper, F Altmann, D van Sinderen, C A Akdis, L O'Mahony
Interactions between the host and the microbiota are thought to significantly influence immunological tolerance mechanisms at mucosal sites. We recently described that the loss of an exopolysaccharide (EPS) from Bifidobacterium longum 35624™ eliminated its protective effects in colitis and respiratory allergy murine models. Our goal was to investigate the immune response to purified EPS from B. longum 35624, determine if it has protective effects within the lung and identify the protective mechanisms. Isolated EPS from B...
May 4, 2018: Beneficial Microbes
https://www.readbyqxmd.com/read/29704322/macrophage-phenotype-in-the-epigallocatechin-3-gallate-egcg-modified-collagen-determines-foreign-body-reaction
#6
Chenyu Chu, Li Liu, Yufei Wang, Shimin Wei, Yuanjing Wang, Yi Man, Yili Qu
Collagen has been widely used in guided bone regeneration, and the implantation of collagen membranes will elicit the foreign body reaction (FBR). The imbalance of FBR often leads to failure of dental implants. Therefore, modulation of the FBR after implantation of collagen membranes becomes increasingly important. Macrophages, pivotal in FBR, have been distinguished into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Epigallocatechin-3-gallate (EGCG)-modified collagen membranes have been previously shown to regulate secretion of inflammatory factors...
April 28, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29651051/collagen-iv-conveyed-signals-can-regulate-chemokine-production-and-promote-liver-metastasis
#7
George Vaniotis, Roni F Rayes, Shu Qi, Simon Milette, Ni Wang, Stephanie Perrino, France Bourdeau, Hanna Nyström, Yi He, Nathalie Lamarche-Vane, Pnina Brodt
Liver metastases remain a major cause of death from gastrointestinal tract cancers as well as from other malignancies such as breast and lung carcinomas and melanoma. Understanding the underlying biology is essential for the design of effective targeted therapies. We previously reported that collagen IV α1/α2 overexpression in non-metastatic lung carcinoma (M27colIV ) cells increased their metastatic ability, specifically to the liver and documented high collagen IV levels in surgical resections of liver metastases from diverse tumor types...
April 13, 2018: Oncogene
https://www.readbyqxmd.com/read/29607536/dp1-receptor-signaling-prevents-the-onset-of-intrinsic-apoptosis-in-eosinophils-and-functions-as-a-transcriptional-modulator
#8
Miriam Peinhaupt, David Roula, Anna Theiler, Miriam Sedej, Rudolf Schicho, Gunther Marsche, Eva M Sturm, Ian Sabroe, Marc E Rothenberg, Akos Heinemann
Prostaglandin (PG) D2 is the ligand for the G-protein coupled receptors DP1 (D-type prostanoid receptor 1) and DP2 (also known as chemoattractant receptor homologous molecule, expressed on Th2 cells; CRTH2). Both, DP1 and DP2 are expressed on the cellular surface of eosinophils; although it has become quite clear that PGD2 induces eosinophil migration mainly via DP2 receptors, the role of DP1 in eosinophil responses has remained elusive. In this study, we addressed how DP1 receptor signaling complements the pro-inflammatory effects of DP2...
April 1, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29547639/interleukin-4-activated-macrophages-mediate-immunity-to-filarial-helminth-infection-by-sustaining-ccr3-dependent-eosinophilia
#9
Joseph D Turner, Nicolas Pionnier, Julio Furlong-Silva, Hanna Sjoberg, Stephen Cross, Alice Halliday, Ana F Guimaraes, Darren A N Cook, Andrew Steven, Nico Van Rooijen, Judith E Allen, Stephen J Jenkins, Mark J Taylor
Eosinophils are effectors in immunity to tissue helminths but also induce allergic immunopathology. Mechanisms of eosinophilia in non-mucosal tissues during infection remain unresolved. Here we identify a pivotal function of tissue macrophages (Mϕ) in eosinophil anti-helminth immunity using a BALB/c mouse intra-peritoneal Brugia malayi filarial infection model. Eosinophilia, via C-C motif chemokine receptor (CCR)3, was necessary for immunity as CCR3 and eosinophil impairments rendered mice susceptible to chronic filarial infection...
March 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29497397/elevated-plasma-chemokines-for-eosinophils-in-neuromyelitis-optica-spectrum-disorders-during-remission
#10
Yanping Tong, Tao Yang, Jingwen Wang, Tianyou Zhao, Lei Wang, Yuezhi Kang, Cuicui Cheng, Yongping Fan
Background: A prominent pathological feature of neuromyelitis optica spectrum disorders (NMOSD) is markedly greater eosinophilic infiltration than that seen in other demyelinating diseases, like multiple sclerosis (MS). Eosinophils express the chemokine receptor CCR3, which is activated by eotaxins (CCL11/eotaxin-1, CCL24/eotaxin-2, CCL26/eotaxin-3) and CCL13 [monocyte chemoattractant protein (MCP)-4]. Moreover, CCL13 is part of the chemokine set that activates CCR2. The present study aimed to evaluate plasma levels of eotaxins (CCL11, CCL24, and CCL26) and MCPs (CCL13, CCL2, CCL8, and CCL7) in patients with NMOSD during remission...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29467297/eosinophil-depletion-suppresses-radiation-induced-small-intestinal-fibrosis
#11
Naoki Takemura, Yosuke Kurashima, Yuki Mori, Kazuki Okada, Takayuki Ogino, Hideki Osawa, Hirosih Matsuno, Lamichhane Aayam, Satoshi Kaneto, Eun Jeong Park, Shintaro Sato, Kouta Matsunaga, Yusuke Tamura, Yasuo Ouchi, Yutaro Kumagai, Daichi Kobayashi, Yutaka Suzuki, Yoshichika Yoshioka, Junichi Nishimura, Masaki Mori, Ken J Ishii, Mark E Rothenberg, Hiroshi Kiyono, Shizuo Akira, Satoshi Uematsu
Radiation-induced intestinal fibrosis (RIF) is a serious complication after abdominal radiotherapy for pelvic tumor or peritoneal metastasis. Herein, we show that RIF is mediated by eosinophil interactions with α-smooth muscle actin-positive (α-SMA+ ) stromal cells. Abdominal irradiation caused RIF especially in the submucosa (SM) of the small intestine, which was associated with the excessive accumulation of eosinophils in both human and mouse. Eosinophil-deficient mice showed markedly ameliorated RIF, suggesting the importance of eosinophils...
February 21, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29464057/construction-of-key-signal-regulatory-network-in-metastatic-colorectal-cancer
#12
Lu Qi, Yanqing Ding
There are many stages in the development and metastasis of colorectal cancer (CRC). In this study, we compared the differential expression genes in different stages of metastatic CRC. Then, we screened the continuously up-regulated genes and the continuously down-regulated genes that were associated with the development and metastasis of CRC. After analyzing the intersection of differential expression genes in each stage, we screened the continuously up-regulated genes and deviated genes in the extracellular matrix and the continuously down-regulated genes and deviated genes in the mitochrondia of CRC...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29457550/mir-505-3p-controls-chemokine-receptor-up-regulation-in-macrophages-role-in-familial-hypercholesterolemia
#13
Rafael Escate, Pedro Mata, Jose Maria Cepeda, Teresa Padró, Lina Badimon
Familial hypercholesterolemia (FH) conveys a high risk of premature atherosclerosis as a result of lifelong exposure to high LDL cholesterol levels that are not fully reduced by standard-of-care lipid-lowering treatment. Inflammatory mediators have played a role in the progression of atherosclerotic lesions. Here, we investigated whether innate immunity cells in patients with FH have a specific proinflammatory phenotype that is distinct from that of cells in normal participants. To this end, miR-505-3p-a microRNA related to chronic inflammation-and its target genes were investigated in monocyte-derived macrophages (MACs) of patients with FH (FH-MACs) and non-FH controls (co-MACs)...
February 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29451337/eosinophil-derived-exosomes-contribute-to-asthma-remodelling-by-activating-structural-lung-cells
#14
J A Cañas, B Sastre, J M Rodrigo-Muñoz, M Fernández-Nieto, P Barranco, S Quirce, J Sastre, V Del Pozo
BACKGROUND: Eosinophils, a central factor in asthma pathogenesis, have the ability to secrete exosomes. However, the precise role played by exosomes in the biological processes leading up to asthma has not been fully defined. OBJECTIVE: We hypothesized that exosomes released by eosinophils contribute to asthma pathogenesis by activating structural lung cells. METHODS: Eosinophils from asthmatic patients and healthy volunteers were purified from peripheral blood, and exosomes were isolated from eosinophils of asthmatic and healthy individuals...
February 16, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29425374/epigenome-wide-association-study-of-dna-methylation-in-narcolepsy-an-integrated-genetic-and-epigenetic-approach
#15
Mihoko Shimada, Taku Miyagawa, Hiromi Toyoda, Katsushi Tokunaga, Makoto Honda
Narcolepsy with cataplexy, which is a hypersomnia characterized by excessive daytime sleepiness and cataplexy, is a multifactorial disease caused by both genetic and environmental factors. Several genetic factors including HLA-DQB1*06:02 have been identified; however, the disease etiology is still unclear. Epigenetic modifications, such as DNA methylation, have been suggested to play an important role in the pathogenesis of complex diseases. Here, we examined DNA methylation profiles of blood samples from narcolepsy and healthy control individuals and performed an epigenome-wide association study (EWAS) to investigate methylation loci associated with narcolepsy...
April 1, 2018: Sleep
https://www.readbyqxmd.com/read/29423947/the-effects-of-a-ccr3-inhibitor-axp1275-on-allergen-induced-airway-responses-in-adults-with-mild-to-moderate-atopic-asthma
#16
G M Gauvreau, J M FitzGerald, L P Boulet, R M Watson, L Hui, H Villineuve, T X Scime, A R Schlatman, C Obminski, J Kum, S Boehme, T W Ly, K B Bacon, P M O'Byrne
BACKGROUND: CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity. OBJECTIVE: This proof-of-mechanism study examined the effect of AXP1275, an oral, small-molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge. METHODS: Twenty-one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double-blind cross-over study to compare early and late allergen-induced asthmatic responses, methacholine PC20 , blood and sputum eosinophils and exhaled nitric oxide after 2 weeks of treatment with once-daily doses of AXP1275 (50 mg) or placebo...
April 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29377961/shared-and-organism-specific-host-responses-to-childhood-diarrheal-diseases-revealed-by-whole-blood-transcript-profiling
#17
Hannah A DeBerg, Mussaret B Zaidi, Matthew C Altman, Prasong Khaenam, Vivian H Gersuk, Freddy D Campos, Iza Perez-Martinez, Mario Meza-Segura, Damien Chaussabel, Jacques Banchereau, Teresa Estrada-Garcia, Peter S Linsley
Globally, diarrheal diseases are a leading cause of death in children under five and disproportionately affect children in developing countries. Children who contract diarrheal diseases are rarely screened to identify the etiologic agent due to time and cost considerations associated with pathogen-specific screening and hence pathogen-directed therapy is uncommon. The development of biomarkers to rapidly identify underlying pathogens could improve treatment options and clinical outcomes in childhood diarrheal diseases...
2018: PloS One
https://www.readbyqxmd.com/read/29338773/chemokine-ligand-receptor-interactions-critically-regulate-cutaneous-wound-healing
#18
Erich Bünemann, Norman-Philipp Hoff, Bettina Alexandra Buhren, Ulrike Wiesner, Stephan Meller, Edwin Bölke, Anja Müller-Homey, Robert Kubitza, Thomas Ruzicka, Albert Zlotnik, Bernhard Homey, Peter Arne Gerber
BACKGROUND: Wound healing represents a dynamic process involving directional migration of different cell types. Chemokines, a family of chemoattractive proteins, have been suggested to be key players in cell-to-cell communication and essential for directed migration of structural cells. Today, the role of the chemokine network in cutaneous wound healing is not fully understood. Unraveling the chemokine-driven communication pathways in this complex process could possibly lead to new therapeutic strategies in wound healing disorders...
January 16, 2018: European Journal of Medical Research
https://www.readbyqxmd.com/read/29334431/activation-state-of-circulating-eosinophils-in-nasal-polyposis
#19
Vincent Dupuch, Arlette Tridon, Sylvie Ughetto, Stéphane Walrand, Benjamin Bonnet, Claude Dubray, Aude Virlogeux, Marie-Paule Vasson, Nicolas Saroul, Thierry Mom, Laurent Gilain, Bertrand Evrard
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease with an uncertain pathophysiology. It is characterized by polyps rich in eosinophils, with an activation status already investigated at the tissue level. In a group of CRSwNP patients, we assessed the activation status of circulating eosinophils in the blood before migration into tissues. METHODS: Thirteen patients with CRSwNP and 16 healthy volunteers were enrolled. Several biologic parameters were studied: blood count of eosinophils; plasma eosinophil cationic protein; oxidative metabolism by chemiluminescence at baseline or when activated by phorbol 12-myristate 13-acetate or platelet-activating factor, with or without interleukin-5 (IL-5); percent of granulosar cells; and mean fluorescence intensity (MFI) by flow cytometry...
January 15, 2018: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/29281969/functional-expression-of-ccl8-and-its-interaction-with-chemokine-receptor-ccr3
#20
Baosheng Ge, Jiqiang Li, Zhijin Wei, Tingting Sun, Yanzhuo Song, Naseer Ullah Khan
BACKGROUND: Chemokines and their cognate receptors play important role in the control of leukocyte chemotaxis, HIV entry and other inflammatory diseases. Developing an effcient method to investigate the functional expression of chemokines and its interactions with specific receptors will be helpful to asses the structural and functional characteristics as well as the design of new approach to therapeutic intervention. RESULTS: By making systematic optimization study of expression conditions, soluble and functional production of chemokine C-C motif ligand 8 (CCL8) in Escherichia coli (E...
December 28, 2017: BMC Immunology
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