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Leon A Sokulsky, Adam M Collison, Scott Nightingale, Anna Le Fevre, Elizabeth Percival, Malcolm R Starkey, Philip M Hansbro, Paul S Foster, Joerg Mattes
INTRODUCTION: Food antigens are common inflammatory triggers in pediatric eosinophilic esophagitis (EoE). TNF-related apoptosis-inducing ligand (TRAIL) promotes eosinophilic inflammation through the upregulation of 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. METHODS: Esophageal mucosal biopsies were collected from children with EoE and controls and assessed for TRAIL and MID-1 protein and mRNA transcript levels...
October 13, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
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
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
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
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
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
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
Latifa Chachi, Mahnaz Abbassian, Adelina Gavrila, Abdulrahman Alzahrani, Omar Tliba, Peter Bradding, Andrew J Wardlaw, Christopher Brightling, Yassine Amrani
BACKGROUND: The mechanisms driving glucocorticoids (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: ASM cells from healthy and severe asthmatic subjects were treated with TNFα and responses to corticosteroids in both cohorts were compared by ELISA, immunoblot, immunohistochemistry and real time PCR...
August 9, 2016: Allergy
Satoshi Matsukura, Yuki Osakabe, Ayaka Sekiguchi, Daisuke Inoue, Yusuke Kakiuchi, Toshitaka Funaki, Yohei Yamazaki, Hiromi Takayasu, Hidetsugu Tateno, Eisuke Kato, Aya Wakabayashi, Makoto Hayashi, Gen Ishii, Fumihiro Yamaguchi, Yutaka Tsuchiya, Keita Kasahara, Hironori Sagara, Fumio Kokubu
BACKGROUND: MicroRNAs are non-coding small RNAs that regulate expression of target genes by binding to 3' untranslated regions. In this study, we used bronchial epithelial cells to investigate in vitro the role of the microRNA miR-155 in the expression of chemokines associated with airway inflammation. miR-155 has previously been reported to regulate allergic inflammation. METHODS: BEAS-2B bronchial epithelial cells were cultured and transfected with mimic or inhibitor oligonucleotides to overexpress or downregulate miR-155, as confirmed by real-time PCR...
September 2016: Allergology International: Official Journal of the Japanese Society of Allergology
Lynn Soong, Nicole L Mendell, Juan P Olano, Dedeke Rockx-Brouwer, Guang Xu, Yenny Goez-Rivillas, Claire Drom, Thomas R Shelite, Gustavo Valbuena, David H Walker, Donald H Bouyer
Scrub typhus is a neglected tropical disease, caused by Orientia tsutsugamushi, a Gram-negative bacterium that is transmitted to mammalian hosts during feeding by Leptotrombidium mites and replicates predominantly within endothelial cells. Most studies of scrub typhus in animal models have utilized either intraperitoneal or intravenous inoculation; however, there is limited information on infection by the natural route in murine model skin or its related early host responses. Here, we developed an intradermal (i...
August 2016: PLoS Neglected Tropical Diseases
Hui Zhao, Flora Kalish, Ronald J Wong, David K Stevenson
Infiltrating myeloid cells in pregnant uteri play critical roles in the establishment of the placenta and maintenance of normal pregnancies. Their recruitment and proliferation are primarily mediated by the interactions of cytokines and chemokines secreted locally with their corresponding receptors. Heme oxygenase-1 (HO-1) has various physiologic properties that contribute to placental vascular development, with deficiencies in HO-1 associated with pregnancy disorders. Here, we investigated the effect of HO-1 on myeloid cell infiltration into pregnant uteri using a partial HO-1-deficient (Het, HO-1(+/-)) mouse model...
July 28, 2016: Journal of Leukocyte Biology
Weisong Zhou, Jian Zhang, Kasia Goleniewska, Daniel E Dulek, Shinji Toki, Dawn C Newcomb, Jacqueline Y Cephus, Robert D Collins, Pingsheng Wu, Mark R Boothby, R Stokes Peebles
Allergic airway diseases are immune disorders associated with heightened type 2 immune responses and IL-5 and IL-13 production at the site of inflammation. We have previously reported that cyclooxygenase (COX) inhibition by indomethacin augmented allergic airway inflammation in a STAT6-independent manner. However, the key COX product(s) responsible for restraining indomethacin-mediated STAT6-independent allergic inflammation is unknown. In this study, using the mouse model of OVA-induced allergic airway inflammation, we identified that PGI2 receptor (IP) signaling was critical for indomethacin-induced, STAT6-independent proallergic effects...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Fábio Vitarelli Marinho, Clarice Carvalho Alves, Sara C de Souza, Cintia M G da Silva, Geovanni D Cassali, Sergio C Oliveira, Lucila G G Pacifico, Cristina T Fonseca
BACKGROUND: Previous studies have demonstrated that S. mansoni infection and inoculation of the parasite eggs and antigens are able to modulate airways inflammation induced by OVA in mice. This modulation was associated to an enhanced production of interleukin-10 and to an increased number of regulatory T cells. The S. mansoni schistosomulum is the first stage to come into contact with the host immune system and its tegument represents the host-parasite interface. The schistosomula tegument (Smteg) has never been studied in the context of modulation of inflammatory disorders, although immune evasion mechanisms take place in this phase of infection to guarantee the persistence of the parasite in the host...
2016: PloS One
Amy R Cameron, Vicky L Morrison, Daniel Levin, Mohapradeep Mohan, Calum Forteath, Craig Beall, Alison D McNeilly, David J K Balfour, Terhi Savinko, Aaron K F Wong, Benoit Viollet, Kei Sakamoto, Susanna C Fagerholm, Marc Foretz, Chim C Lang, Graham Rena
RATIONALE: The diabetes mellitus drug metformin is under investigation in cardiovascular disease, but the molecular mechanisms underlying possible benefits are poorly understood. OBJECTIVE: Here, we have studied anti-inflammatory effects of the drug and their relationship to antihyperglycemic properties. METHODS AND RESULTS: In primary hepatocytes from healthy animals, metformin and the IKKβ (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-α-dependent IκB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1β, and CXCL1/2 (C-X-C motif ligand 1/2)...
August 19, 2016: Circulation Research
Astrid Olsnes Kittang, Kristoffer Sand, Annette Katharina Brenner, Kristin Paulsen Rye, Øystein Bruserud
INTRODUCTION: Myelodysplastic syndromes (MDS) are characterized by bone marrow failure due to disturbed bone marrow maturation. MDS is associated with increased risk of transformation to acute myeloid leukemia (AML) and features of immunological dysregulation. MATERIALS AND METHODS: Serum levels of 47 soluble immune mediators were examined in samples derived from 49 MDS patients (35 low-risk and 14 high-risk) and 23 healthy adults. Our patients represent an unselected population-based cohort...
2016: International Journal of Molecular Sciences
Rosa Mistica C Ignacio, Carla R Gibbs, Eun-Sook Lee, Deok-Soo Son
Obesity is characterized as an accumulation of adipose tissue mass represented by chronic, low-grade inflammation. Obesity-derived inflammation involves chemokines as important regulators contributing to the pathophysiology of obesity-related diseases such as cardiovascular disease, diabetes and some cancers. The obesity-driven chemokine network is poorly understood. Here, we identified the profiles of chemokine signature between human preadipocytes and adipocytes, using PCR arrays and qRT-PCR. Both preadipocytes and adipocytes showed absent or low levels in chemokine receptors in spite of some changes...
June 2016: Immune Network
Haibo Wang, Xiaokun Han, Deeksha Gambhir, Silke Becker, Eric Kunz, Angelina Jingtong Liu, M Elizabeth Hartnett
Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells...
2016: PloS One
Zhengmin Liang, Yangfeng Xu, Xuemei Wen, Haiying Nie, Tingjun Hu, Xiaofeng Yang, Xiao Chu, Jian Yang, Xuming Deng, Jiakang He
Rosmarinic acid (RA) has numerous pharmacologic effects, including anti-oxidant, anti-inflammatory, and analgesic effects. This study aimed to evaluate the preventive activity of RA in a murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice sensitized and challenged with ovalbumin (Ova) were pretreated with RA (5, 10 or 20 mg/kg) at 1 h before Ova challenge. The results demonstrated that RA markedly inhibited increases in inflammatory cells and Th2 cytokines in the bronchoalveolar lavage fluid (BALF), significantly reduced the total IgE and Ova-specific IgE concentrations, and greatly ameliorated airway hyperresponsiveness (AHR) compared with the control Ova-induced mice...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Jeong-Hae Choi, Yeon-Suk Song, Hae-June Lee, Jin-Woo Hong, Gyoo-Cheon Kim
Non-thermal plasma (NTP) has recently been introduced and reported as a novel tool with a range of medicinal and biological roles. Although many studies using NTP have been performed, none has investigated the direct relationship between NTP and immune responses yet. Especially, the effects of NTP on atopic dermatitis (AD) were not been explored. Here, NTP was tested whether it controls immune reactions of AD. NTP treatment was administered to pro-inflammatory cytokine-stimulated keratinocytes and DNCB (2,4-Dinitrochlorobenzene)-induced atopic dermatitis mice, then the immune reactions of cells and skin tissues were monitored...
2016: Scientific Reports
Egon Urgard, Annely Lorents, Mariliis Klaas, Kärt Padari, Janeli Viil, Toomas Runnel, Kent Langel, Külli Kingo, Eric Tkaczyk, Ülo Langel, Toivo Maimets, Viljar Jaks, Margus Pooga, Ana Rebane
The skin is a difficult to access tissue for efficient delivery of large and/or charged macromolecules, including therapeutic DNA and RNA oligonucleotides. Cell-penetrating peptide PepFect6 (PF6) has been shown to be suitable transport vehicle for siRNAs in cell culture and systemically in vivo in mice. MiR-146a is known as anti-inflammatory miRNA that inhibits multiple factors from the nuclear factor (NF)-κB pathway in various cell types, including keratinocytes. In this study, PF6 was shown to form unimodal nanocomplexes with miR-146a mimic that entered into human primary keratinocytes, where miR-146a inhibited the expression of its direct targets from the NF-κB pathway and the genes known to be activated by NF-κB, C-C motif ligand (CCL)5 and interleukin (IL)-8...
August 10, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
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