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https://www.readbyqxmd.com/read/27881708/il-35-suppresses-lipopolysaccharide-induced-airway-eosinophilia-in-ebi3-deficient-mice
#1
Kyosuke Kanai, Ah-Mee Park, Hiroki Yoshida, Ikuo Tsunoda, Osamu Yoshie
EBI3 functions as the subunit of immune-regulatory cytokines, such as IL-27 and IL-35, by pairing with p28 and p35, respectively. We treated wild-type and EBI3-deficient mice with intratracheal administration of LPS and obtained bronchoalveolar lavage fluid (BALF) 24 h later. Although neutrophils were the predominant cells in BALF from both groups of mice, eosinophils were highly enriched and there was increased production of eosinophil-attracting chemokines CCL11 and CCL24 in BALF of EBI3-deficient mice. The bronchial epithelial cells and alveolar macrophages were the major producers of CCL11 and CCL24...
November 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27878757/targeting-ccr3-to-reduce-amyloid-%C3%AE-production-tau-hyperphosphorylation-and-synaptic-loss-in-a-mouse-model-of-alzheimer-s-disease
#2
Chunyan Zhu, Bing Xu, Xiaohong Sun, Qiwen Zhu, Yi Sui
The majority of Alzheimer's disease (AD) patients have a late onset, and chronic neuroinflammation, characterized by glial activation and secretion of pro-inflammatory cytokines and chemokines, plays a role in the pathogenesis of AD. The chemokine CCL11 has been shown to be a causative factor of cognitive decline in the process of aging, but little is known whether it is involved in the pathogenesis of AD. In the present study, we showed that CCR3, the receptor for CCL11, was expressed by hippocampal neurons and treatment of primary hippocampal neuronal cultures (14 days in vitro) with CCL11 resulted in activation of cyclin-dependent kinase 5 and glycogen synthase kinase-3β, associated with elevated tau phosphorylation at multiple sites...
November 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27833910/extracellular-microvesicle-production-by-human-eosinophils-activated-by-inflammatory-stimuli
#3
Praveen Akuthota, Lívia A S Carmo, Kennedy Bonjour, Ryann O Murphy, Thiago P Silva, Juliana P Gamalier, Kelsey L Capron, John Tigges, Vasilis Toxavidis, Virginia Camacho, Ionita Ghiran, Shigeharu Ueki, Peter F Weller, Rossana C N Melo
A key function of human eosinophils is to secrete cytokines, chemokines and cationic proteins, trafficking, and releasing these mediators for roles in inflammation and other immune responses. Eosinophil activation leads to secretion of pre-synthesized granule-stored mediators through different mechanisms, but the ability of eosinophils to secrete extracellular vesicles (EVs), very small vesicles with preserved membrane topology, is still poorly understood. In the present work, we sought to identify and characterize EVs released from human eosinophils during different conditions: after a culturing period or after isolation and stimulation with inflammatory stimuli, which are known to induce eosinophil activation and secretion: CCL11 (eotaxin-1) and tumor necrosis factor alpha (TNF-α)...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27825045/therapeutic-effects-of-rosmarinic-acid-on-airway-responses-in-a-murine-model-of-asthma
#4
Zhengmin Liang, Haiying Nie, Yangfeng Xu, Jianbo Peng, Yun Zeng, Yingyi Wei, Xuemei Wen, Jiaming Qiu, Weiting Zhong, Xuming Deng, Jiakang He
Rosmarinic acid (RA) is an active component of a traditional Chinese herbal medicine. Previously, we reported that RA exerted a strong anti-inflammatory effect in a mouse acute lung injury model. Therefore, we hypothesized that RA might also have potential therapeutic effects in a murine model of asthma. In this study, we aimed to evaluate the anti-asthmatic activity of RA and explored its possible molecular mechanisms of action. Female BALB/c mice that had been sensitized to and challenged with ovalbumin (Ova) were treated with RA (20mg/kg) 1h after challenge...
November 5, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27820933/secretoglobin-superfamily-protein-scgb3a2-alleviates-house-dust-mite-induced-allergic-airway-inflammation-in-mice
#5
Mitsuhiro Yoneda, Lei Xu, Hiroaki Kajiyama, Shuko Kawabe, Jorge Paiz, Jerrold M Ward, Shioko Kimura
BACKGROUND: Secretoglobin (SCGB) 3A2, a novel, lung-enriched, cytokine-like, secreted protein of small molecular weight, was demonstrated to exhibit various biological functions including anti-inflammatory, antifibrotic and growth-factor activities. Anti-inflammatory activity was uncovered using the ovalbumin-induced allergic airway inflammation model. However, further validation of this activity using knockout mice in a different allergic inflammation model is necessary in order to establish the antiallergic inflammatory role for this protein...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27820779/bruton-s-tyrosine-kinase-inhibition-attenuates-liver-damage-in-a-mouse-warm-ischemia-and-reperfusion-model
#6
T Palumbo, K Nakamura, C Lassman, Y Kidani, S J Bensinger, R W Busuttil, J W Kupiec-Weglinski, A Zarrinpar
BACKGROUND: Bruton's tyrosine kinase (Btk) is a central player in multiple signaling pathways of lymphoid and myeloid cells. Myeloid cells are crucial early effectors in organ ischemia/reperfusion injury (IRI). BTKB66 is a selective, irreversible inhibitor of Btk. In this study, we hypothesized that Btk inhibition would reduce hepatocellular injury in a murine model of liver warm hepatic ischemia and reperfusion. METHODS: First, BTKB66 was tested in in vitro models of LPS-mediated neutrophil and macrophage activation...
November 3, 2016: Transplantation
https://www.readbyqxmd.com/read/27795621/ccr9-is-a-key-regulator-of-early-phases-of-allergic-airway-inflammation
#7
C López-Pacheco, G Soldevila, G Du Pont, R Hernández-Pando, E A García-Zepeda
Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/27794000/airway-epithelial-kif3a-regulates-th2-responses-to-aeroallergens
#8
Premkumar Vummidi Giridhar, Sheila M Bell, Anusha Sridharan, Priya Rajavelu, Joseph A Kitzmiller, Cheng-Lun Na, Matthew Kofron, Eric B Brandt, Mark Ericksen, Anjaparavanda P Naren, Changsuk Moon, Gurjit K Khurana Hershey, Jeffrey A Whitsett
KIF3A, the gene encoding kinesin family member 3A, is a susceptibility gene locus associated with asthma; however, mechanisms by which KIF3A might influence the pathogenesis of the disorder are unknown. In this study, we deleted the mouse Kif3a gene in airway epithelial cells. Both homozygous and heterozygous Kif3a gene-deleted mice were highly susceptible to aeroallergens from Aspergillus fumigatus and the house dust mite, resulting in an asthma-like pathology characterized by increased goblet cell metaplasia, airway hyperresponsiveness, and Th2-mediated inflammation...
December 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27780270/placental-chemokine-receptor-d6-is-functionally-impaired-in-pre-eclampsia
#9
Chiara Tersigni, Fiorella Di Nicuolo, Giuseppe Maulucci, Alessandro Rolfo, Domenica Giuffrida, Manuela Veglia, Marco De Spirito, Giovanni Scambia, Tullia Todros, Nicoletta Di Simone
BACKGROUND: Pre-eclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality worldwide. It is defined by new onset of hypertension and proteinuria after the 20th week of gestation and characterized by systemic exaggerated inflammatory response. D6 is a chemokines scavenger receptor that binds with high affinity CC chemokines, internalizes and targets the ligands for degradation. It is expressed in trophoblast-derived tissues and prevents excessive placenta leukocyte infiltration...
2016: PloS One
https://www.readbyqxmd.com/read/27776524/pulsed-high-dose-dexamethasone-modulates-th1-th2-chemokine-imbalance-in-immune-thrombocytopenia
#10
Zongtang Liu, Meiying Wang, Shufen Zhou, Ji Ma, Yan Shi, Jun Peng, Ming Hou, Chengshan Guo
BACKGROUND: Chemokines and chemokine receptors play important roles in autoimmune diseases; however, their role in immune thrombocytopenia (ITP) is unclear. High-dose dexamethasone (HD-DXM) may become a first-line therapy for adult patients with ITP, but the effect of HD-DXM on chemokines in ITP patients is unknown. Our aim was to investigate the mechanism of pulsed HD-DXM for management of ITP, specifically regarding the chemokine pathways. METHODS: Th1-/Th2-associated chemokine and chemokine receptor profiles in ITP patients before and after pulsed HD-DXM was studied...
October 24, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27768790/thy-1-regulates-vegf-mediated-choroidal-endothelial-cell-activation-and-migration-implications-in-neovascular-age-related-macular-degeneration
#11
Haibo Wang, Xiaokun Han, Eric Kunz, M Elizabeth Hartnett
Purpose: This study addresses the hypothesis that age-related stresses upregulate Thy-1 in choroidal endothelial cells (CECs) and contribute to CEC activation and migration, processes important in choroidal neovascularization (CNV). Methods: Measurements were made of Thy-1 protein (Western blot) in CECs and Thy-1 mRNA (real time quantitative PCR) in CECs treated with VEGF, CCL11, or PBS or in RPE/choroids from young or old donors or lasered or nonlasered mice. Immunolabeled Thy-1 in ocular sections was compared from young versus old human donor eyes or those with or without neovascular AMD or from lasered versus nonlasered mice...
October 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27766108/co-exposure-to-zymosan-a-and-heat-inactivated-asian-sand-dust-exacerbates-ovalbumin-induced-murine-lung-eosinophilia
#12
Kaori Sadakane, Takamichi Ichinose, Masataka Nishikawa, Hirohisa Takano, Takayuki Shibamoto
BACKGROUND: Epidemiological studies have implicated Asian sand dust (ASD) in the increased prevalence of respiratory disorders, including asthma. It has been observed that fungal elements such as β-glucan can be adsorbed onto ASD. In the present study, the exacerbating effect of the combined exposure to zymosan A (ZymA) containing yeast β-glucan and heat-inactivated ASD on ovalbumin (OVA)-induced murine lung eosinophilia was investigated. METHODS: BALB/c mice were repeatedly instilled intratracheally with one of eight immunogenic formulations consisting of various combinations of (1) ZymA, (2) ASD that was briefly heated to remove organic substances (H-ASD), and (3) OVA in normal saline, or each of the above alone...
2016: Allergy, Asthma, and Clinical Immunology
https://www.readbyqxmd.com/read/27742702/trail-deficiency-and-pp2a-activation-with-salmeterol-ameliorates-egg-allergen-driven-eosinophilic-esophagitis
#13
Leon A Sokulsky, Adam M Collison, Scott Nightingale, Anna Le Fevre, Elizabeth Percival, Malcolm R Starkey, Philip M Hansbro, Paul S Foster, Joerg Mattes
Food antigens are common inflammatory triggers in pediatric eosinophilic esophagitis (EoE). TNF-related apoptosis-inducing ligand (TRAIL) promotes eosinophilic inflammation through the upregulation of the E3 ubiquitin ligase Midline (MID)-1 and subsequent downregulation of protein phosphatase 2A (PP2A), but the role of this pathway in EoE that is experimentally induced by repeated food antigen challenges has not been investigated. Esophageal mucosal biopsies were collected from children with EoE and controls and assessed for TRAIL and MID-1 protein and mRNA transcript levels...
December 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27664933/an-emerging-role-for-eotaxins-in-neurodegenerative-disease
#14
Amanda K Huber, David A Giles, Benjamin M Segal, David N Irani
Eotaxins are C-C motif chemokines first identified as potent eosinophil chemoattractants. They facilitate eosinophil recruitment to sites of inflammation in response to parasitic infections as well as allergic and autoimmune diseases such as asthma, atopic dermatitis, and inflammatory bowel disease. The eotaxin family currently includes three members: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26). Despite having only ~30% sequence homology to one another, each was identified based on its ability to bind the chemokine receptor, CCR3...
September 21, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27650194/abnormalities-in-chemokine-levels-in-schizophrenia-and-their-clinical-correlates
#15
Suzi Hong, Ellen E Lee, Averria Sirkin Martin, Benchawanna Soontornniyomkij, Virawudh Soontornniyomkij, Cristian L Achim, Chase Reuter, Michael R Irwin, Lisa T Eyler, Dilip V Jeste
Chemokines are promising biomarkers of immune activation and inflammation, but evidence for chemokine abnormalities in schizophrenia and their relationship to clinical factors remains inconclusive. We aimed to understand chemokine-related diagnostic differences and clinical correlates using a comprehensive panel and studying a large, well-characterized sample of adults with and without schizophrenia. We studied 134 outpatients with schizophrenia or schizoaffective disorder and 112 healthy comparison (HC) individuals, 26 to 65years of age...
September 17, 2016: Schizophrenia Research
https://www.readbyqxmd.com/read/27621211/macrophages-and-cardiac-fibroblasts-are-the-main-producers-of-eotaxins-and-regulate-eosinophil-trafficking-to-the-heart
#16
Nicola L Diny, Xuezhou Hou, Jobert G Barin, Guobao Chen, Monica V Talor, Julie Schaub, Stuart D Russell, Karin Klingel, Noel R Rose, Daniela Čiháková
Cardiac manifestations are a major cause of morbidity and mortality in patients with eosinophil-associated diseases. Eosinophils are thought to play a pathogenic role in myocarditis. We investigated the pathways that recruit eosinophils to the heart using a model of eosinophilic myocarditis, in which experimental autoimmune myocarditis (EAM) is induced in IFNγ(-/-) IL-17A(-/-) mice. Two conditions are necessary for efficient eosinophil trafficking to the heart: high eotaxin (CCL11, CCL24) expression in the heart and expression of the eotaxin receptor CCR3 by eosinophils...
September 12, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27604227/parp-inhibition-treatment-in-a-nonconventional-experimental-mouse-model-of-chronic-asthma
#17
Raffaela Zaffini, Rosanna Di Paola, Salvatore Cuzzocrea, Marta Menegazzi
Allergic asthma is an immunological disease that occurs as a consequence of aeroallergen exposure. Inhibition of poly(ADP-ribose) polymerases (PARPs) in conventional models of asthma-like reaction has emerged as an effective anti-inflammatory and airway remodeling intervention. In a house dust mite (HDM) exposure mouse model, we investigated the impact of PARP inhibition on allergic airway inflammation, sensitization, and remodeling. Mice were intranasally exposed to a HDM extract for 5 days per week for up to 5 weeks...
September 7, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27598436/a-chronic-rhinosinusitis-derived-isolate-of-pseudomonas-aeruginosa-induces-acute-and-pervasive-effects-on-the-murine-upper-airway-microbiome-and-host-immune-response
#18
Emily K Cope, Andrew N Goldberg, Steven D Pletcher, Susan V Lynch
BACKGROUND: Diverse microbial communities colonize healthy sinus mucosa and specific species within these communities are capable of protecting the host from pathogenic infection. However, little is known of the dynamics of upper airway infection and the role of the sinus mucosal microbiome in short- and longer-term outcomes using clinical isolates from patients with chronic rhinosinusitis. METHODS: We examine microbiome and immune dynamics after murine sinus infection with Pseudomonas aeruginosa EC1, isolated previously from a chronic rhinosinusitis patient...
September 6, 2016: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/27568862/coagulin-l-ameliorates-tlr4-induced-oxidative-damage-and-immune-response-by-regulating-mitochondria-and-nox-derived-ros
#19
Sukka Santosh Reddy, Parul Chauhan, Preeti Maurya, Deepika Saini, Prem Prakash Yadav, Manoj Kumar Barthwal
Withanolides possess diverse biological and pharmacological activity but their immunomodulatory function is less realized. Hence, coagulin-L, a withanolide isolated from Withania coagulans Dunal has been studied for such an effect in human and murine cells, and mice model. Coagulin-L (1, 3, 10μM) exhibited immunomodulatory effect by suppressing TLR4 induced immune mediators such as cytokines (GMCSF, IFNα, IFNγ, IL-1α, IL-1Rα, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17), chemokines (IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10, KC, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, eotaxin/CCL11), growth factors (FGF-basic, VEGF), nitric oxide and intracellular superoxide...
October 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27501780/protein-phosphatase-5-mediates-corticosteroid-insensitivity-in-airway-smooth-muscle-in-patients-with-severe-asthma
#20
L Chachi, M Abbasian, A Gavrila, A Alzahrani, O Tliba, P Bradding, A J Wardlaw, C Brightling, Y Amrani
BACKGROUND: The mechanisms driving glucocorticoid (GC) insensitivity in patients with severe asthma are still unknown. Recent evidence suggests the existence of GC-insensitive pathways in airway smooth muscle (ASM) caused by a defect in GC receptor (GRα) function. We examined whether other mechanisms could potentially explain the reduced sensitivity of ASM cells to GC in severe asthmatics. METHODS: Airway smooth muscle cells from healthy and severe asthmatic subjects were treated with TNF-α and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real-time PCR...
August 9, 2016: Allergy
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