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https://www.readbyqxmd.com/read/28615221/coronin-1a-a-novel-player-in-integrin-biology-controls-neutrophil-trafficking-in-innate-immunity
#1
Robert Pick, Daniela Begandt, Thomas J Stocker, Melanie Salvermoser, Sarah Thome, Ralph T Böttcher, Eloi Montanez, Ute Harrison, Ignasi Forné, Alexander G Khandoga, Raffaele Coletti, Ludwig T Weckbach, Doris Brechtefeld, Rainer Haas, Axel Imhof, Steffen Massberg, Markus Sperandio, Barbara Walzog
Trafficking of polymorphonuclear neutrophils (PMNs) during inflammation critically depends on the β2 integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18). Here, we identify Coronin 1A (Coro1A) as a novel regulator of β2 integrins that interacts with the cytoplasmic tail of CD18 and is crucial for induction of PMN adhesion and post-adhesion events, including adhesion strengthening, spreading, and migration under flow conditions. Transition of PMN rolling to firm adhesion critically depends on Coro1A by regulating the accumulation of high affinity LFA-1 in focal zones of adherent cells...
June 14, 2017: Blood
https://www.readbyqxmd.com/read/28611472/cd11a-icam-1-blockade-combined-with-il-2-targeting-therapy-causes-a-paradoxical-acceleration-of-type-1-diabetes
#2
Ekua W Brenu, Timothy J Bartley, Casey M Wright, Emma Hamilton-Williams
Enhancement of regulatory T cell (Treg) function is the goal of many immunotherapies aimed at treating type 1 diabetes (T1D). The use of IL-2 is hindered by its effects on other populations such as effector T cells and NK cells. Combination therapies aimed at suppressing effector T cells while using IL-2 to expand Tregs could be beneficial and have been trialed in T1D patients. We have investigated a combination therapy using IL-2 and αCD11a blocking antibody to simultaneously expand Tregs and suppress the activation and migration of autoreactive T cells...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28490464/perioperative-cox-2-and-beta-adrenergic-blockade-improves-metastatic-biomarkers-in-breast-cancer-patients-in-a-phase-ii-randomized-trial
#3
Lee Shaashua, Maytal Shabat-Simon, Rita Haldar, Pini Matzner, Oded Zmora, Moshe Shabtai, Eran Sharon, Tanir Allweis, Iris Barshack, Lucile Hayman, Jesusa M G Arevalo, Jeffrey Ma, Maya Horowitz, Steve W Cole, Shamgar Ben-Eliyahu
<br /> <p>Translational studies suggest that excess perioperative release of catecholamines and prostaglandins may facilitate metastasis and reduce disease-free survival. This trial tested the combined perioperative blockade of these pathways in breast cancer patients.</p> <br />Experimental Design: <br /> <p>In a randomized placebo-controlled biomarker trial, 38 early-stage breast cancer patients received 11 days of perioperative treatment with a beta-adrenergic antagonist (propranolol) and a cyclooxygenase-2 (COX-2) inhibitor (etodolac), beginning five days before surgery...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28445705/mutation-characterization-and-heterodimer-analysis-of-patients-with-leukocyte-adhesion-deficiency-including-one-novel-mutation
#4
Shahram Teimourian, Martin De Boer, Dirk Roos, Anna Isaian, Ehsan Moghanloo, Sharhzad Lashkary, Bita Hassani, Hasan Mollanoori, Vahid Babaei, Asaad Azarnezhad
BACKGROUND AND AIM: Leukocyte adhesion deficiency type 1 (LAD-I) is a rare, autosomal recessive disorder of neutrophil migration, characterized by severe, recurrent bacterial infections, inadequate pus formation and impaired wound healing. The ITGB2 gene encodes the β2 integrin subunit (CD18) of the leukocyte adhesion cell molecules, and mutations in this gene cause LAD-I. The aim of the current study was to investigate the mutations in patients diagnosed with LAD-I and functional studies of the impact of two previously reported and a novel mutation on the expression of the CD18/CD11a heterodimer...
April 23, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28430662/histone-demethylase-jmjd3-regulates-cd11a-expression-through-changes-in-histone-h3k27-tri-methylation-levels-in-cd4-t-cells-of-patients-with-systemic-lupus-erythematosus
#5
Heng Yin, Haijing Wu, Ming Zhao, Qing Zhang, Hai Long, Siqi Fu, Qianjin Lu
Aberrant CD11a overexpression in CD4+ T cells induces T cell auto-reactivity, which is an important factor for systemic lupus erythematosus (SLE) pathogenesis. Although many studies have focused on CD11a epigenetic regulation, little is known about histone methylation. JMJD3, as a histone demethylase, is capable of specifically removing the trimethyl group from the H3K27 lysine residue, triggering target gene activation. Here, we examined the expression and function of JMJD3 in CD4+ T cells from SLE patients...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28370402/immunophenotype-of-neutrophils-in-oral-squamous-cell-carcinoma-patients
#6
Patrícia Carlos Caldeira, Érica Leandro Marciano Vieira, Alexandre Andrade Sousa, Antônio Lúcio Teixeira, Maria Cássia Ferreira Aguiar
BACKGROUND: The aim was to explore the immunophenotype of neutrophils and lymphocytes and the inflammatory mediators in patients with oral squamous cell carcinoma, comparing with controls; and to associate with clinicopathological data. METHODS: Blood was collected from 13 patients and 13 controls. The immunophenotype of neutrophils (CD66b, CD16, CD11a, arginase-1), T lymphocytes (CD4, CD8) and the intracellular cytokine production (IL-10, TNF, IFN-γ) was evaluated by flow cytometry...
March 29, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28343767/neural-cell-adhesion-molecule-expression-in-dilated-cardiomyopathy-is-associated-with-intramyocardial-inflammation-and-hypertrophy
#7
Karsten Ostermann, Heinz-Peter Schultheiss, Michel Noutsias
Chronic intramyocardial inflammation (inflammatory cardiomyopathy/DCMi) is linked to the pathogenesis of dilated cardiomyopathy (DCM). Neural cell adhesion molecule (NCAM) is involved in orchestrating cardiac muscle morphogenesis, but is down-regulated after embryogenesis. We investigated NCAM expression in adult DCM hearts, its possible association with DCMi-parameters, and with cardiomyocyte hypertrophy (CMH). Endomyocardial biopsies (EMBs) from DCM patients (n=85; n=37 females; age: 48±19years; LVEF <40%) and controls from non-cardiac deaths were immunostained for DCMi markers and for NCAM expression, and quantified by digital image analysis (DIA)...
March 18, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28154998/upregulated-expression-of-substance-p-sp-and-nk1r-in-eczema-and-sp-induced-mast-cell-accumulation
#8
Mengmeng Zhan, Wenjiao Zheng, Qijun Jiang, Zuotao Zhao, Zhiyun Wang, Junling Wang, Huiyun Zhang, Shaoheng He
Substance P (SP) was reported to be associated with eczema and acts as a potent skin mast cell secretagogue. However, little is known of its expression in inflammatory cells in eczema and its ability in induction of mast cell accumulation. In the present study, we investigated expression of SP and neurokinin-1 receptor (NK1R) on peripheral blood leukocytes and mast cells from patients with eczema and influence of SP on mast cell accumulation by using flow cytometry analysis, trans-epithelial cell migration assay and mouse peritoneal model...
February 2, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28129380/the-identification-and-distribution-of-cattle-xcr1-and-xcl1-among-peripheral-blood-cells-new-insights-into-the-design-of-dendritic-cells-targeted-veterinary-vaccine
#9
Kun Li, Guoyan Wei, Yimei Cao, Dong Li, Pinghua Li, Jing Zhang, Huifang Bao, Yingli Chen, Yuanfang Fu, Pu Sun, Xingwen Bai, Xueqing Ma, Zengjun Lu, Zaixin Liu
The chemokine (C motif) receptor 1 (XCR1) and its ligandXCL1 have been intensively studied in the mouse and human immune systems. Here, we determined the molecular characteristics of cattle XCR1 and XCL1 and their distribution among peripheral blood cells. Cattle XCR1 mRNA expression was mainly restricted to CD26+CADM1+CD205+MHCII+CD11b- cells in blood that were otherwise lineage marker negative (lin-); these represented a subset of classic dendritic cells (DCs), not plasmacytoid DCs. Some of these DCs expressed CD11a, CD44, CD80 and CD86, but they did not express CD4, CD8, CD163 or CD172a...
2017: PloS One
https://www.readbyqxmd.com/read/28101472/the-effects-of-hypoxia-on-u937-cell-line-in-mesenchymal-stem-cells-co-culture-system
#10
Mostafa Ejtehadifar, Karim Shamsasenjan, Parvin Akbarzadehlaleh, Sarah Zahedi, Narjes Kazemi
Purpose: Mesenchymal Stem Cells (MSCs) are the most important members of Bone Marrow (BM) milieu. MSCs affect different kinds of cells, particularly malignant cells of hematologic malignancies, but the effects of MSCs are unclear exactly. Here we analyzed the effects of derived Umbilical Cord Blood-MSCs on proliferation, cell death and some surface markers of U937 cell line in a Co-culture system with MSCs. Methods: Here we designed Co-culture systems as a model of BM milieu. We cultured U937 cells on UCB-MSCs and MSCs Conditioned Medium (C...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28063475/characterisation-of-monoclonal-antibodies-specific-for-hamster-leukocyte-differentiation-molecules
#11
Jennifer Rees, David Haig, Victoria Mack, William C Davis
Flow cytometry was used to identify mAbs that recognize conserved epitopes on hamster leukocyte differentiation molecules (hLDM) and also to characterize mAbs developed against hLDM. Initial screening of mAbs developed against LDMs in other species yielded mAbs specific for the major histocompatibility (MHC) II molecule, CD4 and CD18. Screening of sets of mAbs developed against hLDM yielded 22 new mAbs, including additional mAbs to MHC II molecules and mAbs that recognize LDMs expressed on all leukocytes, granulocytes, all lymphocytes, all T cells, a subset of T cells, or on all B cells...
January 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/28000693/consumption-of-a-high-fat-breakfast-on-consecutive-days-alters-preclinical-biomarkers-for-atherosclerosis
#12
B K McFarlin, K C Carpenter, A L Henning, A S Venable
BACKGROUND/OBJECTIVES: Recent research has speculated that the risk of developing atherosclerosis is due to the accumulation of the effects of daily diet choices. The purpose of this study was to examine which of our previously identified preclinical disease risk biomarkers were further elevated when consuming a high-fat (644±50 kcal; 100% recommended dietary allowance for fat), high-calorie (1118±100 kcal; 70% daily caloric needs) breakfast on consecutive days. Young, normal weight females (N=7) participated in this study...
February 2017: European Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/27915349/roles-of-1-25-oh-2d3-and-vitamin-d-receptor-in-the-pathogenesis-of-rheumatoid-arthritis-and-systemic-lupus-erythematosus-by-regulating-the-activation-of-cd4-t-cells-and-the-pkc%C3%AE-erk-signaling-pathway
#13
Xiao-Jie He, Yan Ding, Wei Xiang, Xi-Qiang Dang
BACKGROUND/AIMS: The study aims to elucidate the roles of 1,25(OH)2D3 and vitamin D receptor (VDR) in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) by regulating the activation of CD4+ T cells and the PKCδ/ERK signaling pathway. METHODS: From January 2013 to December 2015, a total of 130 SLE patients, 137 RA patients and 130 healthy controls were selected in this study. Serum levels of 1,25(OH)2D3 and VDR mRNA expression were detected by ELISA and real-time fluorescence quantitative PCR (RT-qPCR)...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27883055/gapmer-cellular-internalization-by-macropinocytosis-induces-sequence-specific-gene-silencing-in-human-primary-t-cells
#14
Mobashar Hussain Urf Turabe Fazil, Seow Theng Ong, Madhavi Latha Somaraju Chalasani, Jian Hui Low, Atish Kizhakeyil, Akshay Mamidi, Carey Fang Hui Lim, Graham D Wright, Rajamani Lakshminarayanan, Dermot Kelleher, Navin Kumar Verma
Post-transcriptional gene silencing holds great promise in discovery research for addressing intricate biological questions and as therapeutics. While various gene silencing approaches, such as siRNA and CRISPR-Cas9 techniques, are available, these cannot be effectively applied to "hard-to-transfect" primary T-lymphocytes. The locked nucleic acid-conjugated chimeric antisense oligonucleotide, called "GapmeR", is an emerging new class of gene silencing molecule. Here, we show that GapmeR internalizes into human primary T-cells through macropinocytosis...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27864142/glycogen-storage-disease-type-ib-neutrophils-exhibit-impaired-cell-adhesion-and-migration
#15
Goo-Young Kim, Young Mok Lee, Joon Hyun Kwon, Hyun Sik Jun, Janice Chou
Glycogen storage disease type Ib (GSD-Ib), characterized by impaired glucose homeostasis, neutropenia, and neutrophil dysfunction, is an inherited autosomal recessive disorder caused by a deficiency in the glucose-6-phosphate transporter (G6PT). Neutrophils play an essential role in the defense against invading pathogens. The recruitment of neutrophils towards the inflammation sites in response to inflammatory stimuli is a tightly regulated process involving rolling, adhesion, and transmigration. In this study, we investigated the role of G6PT in neutrophil adhesion and migration using in vivo and in vitro models...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27818457/isolation-and-characterization-of-equine-dental-pulp-stem-cells-derived-from-thoroughbred-wolf-teeth
#16
Shingo Ishikawa, Chie Horinouchi, Daiki Murata, Shota Matsuzaki, Kazuhiro Misumi, Yohei Iwamoto, Kenji Korosue, Seiji Hobo
Mesenchymal stem cells (MSCs) are adult multipotent stem cells that are capable of self-renewal and differentiation into multiple cell lineages. Methods for cell therapy using MSCs have been developed in equine medicine. Recently, human dental pulp stem cells (DPSCs) have drawn much attention owing to their trophic factor producing ability and minimally invasive collection methods. However, there have been no reports on equine dental pulp-derived cells (eDPCs). Therefore, the aim of this study was to isolate and characterize the eDPCs from discarded wolf teeth...
January 20, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27818315/il-20-promotes-epithelial-healing-of-the-injured-mouse-cornea
#17
Wanyu Zhang, Sri Magadi, Zhijie Li, C Wayne Smith, Alan R Burns
After corneal epithelial injury, the ensuing inflammatory response is necessary for efficient wound healing. While beneficial healing effects are attributed to recruited neutrophils and platelets, dysregulated inflammation (too little or too much) is associated with impaired wound healing. The purpose of this study was to use an established C57BL/6J mouse model of corneal injury to evaluate the potential modulatory role of interleukin-20 (IL-20) on the inflammatory and healing responses to epithelial wounding...
January 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/27795356/mitogen-activated-protein-kinase-2-signaling-shapes-macrophage-plasticity-in-aggregatibacter-actinomycetemcomitans-induced-bone-loss
#18
Bethany A Herbert, Heidi M Steinkamp, Matthias Gaestel, Keith L Kirkwood
Aggregatibacter actinomycetemcomitans is associated with aggressive periodontal disease, which is characterized by inflammation-driven alveolar bone loss. A. actinomycetemcomitans activates the p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase 2 (MK2) stress pathways in macrophages that are involved in host responses. During the inflammatory process in periodontal disease, chemokines are upregulated to promote recruitment of inflammatory cells. The objective of this study was to determine the role of MK2 signaling in chemokine regulation during A...
January 2017: Infection and Immunity
https://www.readbyqxmd.com/read/27731313/targeted-delivery-of-an-anti-inflammatory-pde4-inhibitor-to-immune-cells-via-an-antibody-drug-conjugate
#19
Shan Yu, Aaron D Pearson, Reyna Kv Lim, David T Rodgers, Sijia Li, Holly B Parker, Meredith Weglarz, Eric N Hampton, Michael J Bollong, Jiayin Shen, Claudio Zambaldo, Danling Wang, Ashley K Woods, Timothy M Wright, Peter G Schultz, Stephanie A Kazane, Travis S Young, Matthew S Tremblay
Phosphodiesterase 4 (PDE4) inhibitors are approved for the treatment of some moderate to severe inflammatory conditions. However, dose-limiting side effects in the central nervous system and gastrointestinal tract, including nausea, emesis, headache, and diarrhea, have impeded the broader therapeutic application of PDE4 inhibitors. We sought to exploit the wealth of validation surrounding PDE4 inhibition by improving the therapeutic index through generation of an antibody-drug conjugate (ADC) that selectively targets immune cells through the CD11a antigen...
December 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/27720134/l-plastin-regulates-the-stability-of-the-immune-synapse-of-naive-and-effector-t-cells
#20
REVIEW
Guido Wabnitz, Emre Balta, Yvonne Samstag
T-cells need to be tightly regulated during their activation and effector phase to assure an appropriate defence against cancer or pathogens and - vice versa - to avoid autoimmune reactions. Regulatory signals are provided via the immune synapse between T-cells and antigen-presenting cells (APCs) or target cells. The stability and kinetics of immune synapse formation is critical for proper T-cell functions. It requires dynamic rearrangements of the actin cytoskeleton necessary for organized spatio-temporal redistribution of receptors and adhesion molecules...
September 27, 2016: Advances in Biological Regulation
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