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https://www.readbyqxmd.com/read/28205614/cxcr2-deficient-mice-display-macrophage-dependent-exaggerated-acute-inflammatory-responses
#1
Douglas P Dyer, Kenneth Pallas, Laura Medina Ruiz, Fabian Schuette, Gillian J Wilson, Gerard J Graham
CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites and plays prominent roles in inflammatory pathologies and cancer. It has therefore been highlighted as an important therapeutic target. However the success of the therapeutic targeting of CXCR2 is threatened by our relative lack of knowledge of its precise in vivo mode of action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated inflammatory response to cutaneous and peritoneal inflammatory stimuli...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28186102/cancer-cell-secreted-igf2-instigates-fibroblasts-and-bone-marrow-derived-vascular-progenitor-cells-to-promote-cancer-progression
#2
Wen Wen Xu, Bin Li, Xin Yuan Guan, Sookja K Chung, Yang Wang, Yim Ling Yip, Simon Y K Law, Kin Tak Chan, Nikki P Y Lee, Kwok Wah Chan, Li Yan Xu, En Min Li, Sai Wah Tsao, Qing-Yu He, Annie L M Cheung
Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects...
February 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28179147/structural-basis-of-pdz-mediated-chemokine-receptor-cxcr2-scaffolding-by-guanine-nucleotide-exchange-factor-pdz-rhogef
#3
Nicholas Spellmon, Joshua Holcomb, Andrea Niu, Vishakha Choudhary, Xiaonan Sun, Yingxue Zhang, Junmei Wan, Maysaa Doughan, Stephanie Hayden, Fatme Hachem, Joseph Brunzelle, Chunying Li, Zhe Yang
The CXC chemokine receptor 2 (CXCR2) is a G protein coupled receptor mediating interleukin-8 chemotactic signaling and plays an important role in neutrophil mobility and tumor migration. However, efficient CXCR2 signaling requires PDZ domain-mediated scaffolding of signaling complexes at the plasma membrane and functional coupling of the signaling to specific downstream signaling pathways, in which only one PDZ protein has been characterized to interact with CXCR2. Here, we identified five novel CXCR2-binding PDZ-containing proteins, among which PDZ-RhoGEF is of particular interest because this PDZ and RGS-containing guanine nucleotide exchange factor (GEF) is also involved in cell signaling and mobility...
February 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28176455/adiponectin-promotes-human-jaw-bone-marrow-mesenchymal-stem-cell-chemotaxis-via-cxcl1-and-cxcl8
#4
Yinfei Pu, Mengke Wang, Yingying Hong, Yuwei Wu, Zhihui Tang
Adiponectin (APN) is known to promote the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (h-JBMMSCs). However, the underlying mechanism has not been fully elucidated. Previously, we showed that APN could promote h-JBMMSC osteogenesis via APPL1-p38 by up-regulating osteogenesis-related genes. Here, we aimed to determine whether APN could promote h-JBMMSC chemotaxis through CXCL1/CXCL8. The CCK-8, wound healing and transwell assays were used to evaluate the proliferation, migration and chemotaxis of h-JBMMSCs with or without APN treatment...
February 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28159737/stem-and-progenitor-cell-alterations-in-myelodysplastic-syndromes
#5
Aditi Shastri, Britta Will, Ulrich Steidl, Amit Verma
Recent studies have demonstrated that myelodysplastic syndromes (MDS) arise from a small population of disease initiating hematopoietic stem cells (HSCs) that persist and expand through conventional therapies and are major contributors to disease progression and relapse. MDS stem and progenitor cells are characterized by key founder and driver mutations and are enriched for cytogenetic alterations. Quantitative alterations in stem and progenitor numbers are also seen in a stage specific manner in human MDS samples as well as in murine models of the disease...
February 3, 2017: Blood
https://www.readbyqxmd.com/read/28151558/whole-transcriptome-sequencing-identifies-increased-cxcr2-expression-in-pnh-granulocytes
#6
Kohei Hosokawa, Sachiko Kajigaya, Keyvan Keyvanfar, Wangmin Qiao, Yanling Xie, Angelique Biancotto, Danielle M Townsley, Xingmin Feng, Neal S Young
The aetiology of paroxysmal nocturnal haemoglobinuria (PNH) is a somatic mutation in the X-linked phosphatidylinositol glycan class A gene (PIGA), resulting in global deficiency of glycosyl phosphatidylinositol-anchored proteins (GPI-APs). This study applied RNA-sequencing to examine functional effects of the PIGA mutation in human granulocytes. CXCR2 expression was increased in GPI-AP(-) compared to GPI-AP(+) granulocytes. Macrophage migration inhibitory factor, a CXCR2 agonist, was significantly higher in plasma of PNH patients...
February 1, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28129639/ladarixin-a-dual-cxcr1-2-inhibitor-attenuates-experimental-melanomas-harboring-different-molecular-defects-by-affecting-malignant-cells-and-tumor-microenvironment
#7
Daria Marley Kemp, Alyson Pidich, Mary Larijani, Rebecca Jonas, Elizabeth Lash, Takami Sato, Mizue Terai, Maria De Pizzol, Marcello Allegretti, Olga Igoucheva, Vitali Alexeev
CXCR1 and CXCR2 chemokine receptors and their ligands (CXCL1/2/3/7/8) play an important role in tumor progression. Tested to date CXCR1/2 antagonists and chemokine-targeted antibodies were reported to affect malignant cells in vitro and in animal models. Yet, redundancy of chemotactic signals and toxicity hinder further clinical development of these approaches. In this pre-clinical study we investigated the capacity of a novel small molecule dual CXCR1/2 inhibitor, Ladarixin (LDX), to attenuate progression of experimental human melanomas...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28112221/mincle-activation-enhances-neutrophil-migration-and-resistance-to-polymicrobial-septic-peritonitis
#8
Wook-Bin Lee, Ji-Jing Yan, Ji-Seon Kang, Quanri Zhang, Won Young Choi, Lark Kyun Kim, Young-Joon Kim
Sepsis is a systemic inflammatory response to bacterial infection. The therapeutic options for treating sepsis are limited. Impaired neutrophil recruitment into the infection site is directly associated with severe sepsis, but the precise mechanism is unclear. Here, we show that Mincle plays a key role in neutrophil migration and resistance during polymicrobial sepsis. Mincle-deficient mice exhibited lower survival rates in experimental sepsis from cecal ligation and puncture and Escherichia coli-induced peritonitis...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106142/identification-of-lukpq-a-novel-equid-adapted-leukocidin-of-staphylococcus-aureus
#9
Gerrit Koop, Manouk Vrieling, Daniel M L Storisteanu, Laurence S C Lok, Tom Monie, Glenn van Wigcheren, Claire Raisen, Xiaoliang Ba, Nicholas Gleadall, Nazreen Hadjirin, Arjen J Timmerman, Jaap A Wagenaar, Heleen M Klunder, J Ross Fitzgerald, Ruth Zadoks, Gavin K Paterson, Carmen Torres, Andrew S Waller, Anette Loeffler, Igor Loncaric, Armando E Hoet, Karin Bergström, Luisa De Martino, Constança Pomba, Hermínia de Lencastre, Karim Ben Slama, Haythem Gharsa, Emily J Richardson, Edwin R Chilvers, Carla de Haas, Kok van Kessel, Jos A G van Strijp, Ewan M Harrison, Mark A Holmes
Bicomponent pore-forming leukocidins are a family of potent toxins secreted by Staphylococcus aureus, which target white blood cells preferentially and consist of an S- and an F-component. The S-component recognizes a receptor on the host cell, enabling high-affinity binding to the cell surface, after which the toxins form a pore that penetrates the cell lipid bilayer. Until now, six different leukocidins have been described, some of which are host and cell specific. Here, we identify and characterise a novel S...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28063617/corrigendum-to-lipocalin-2-mediates-non-alcoholic-steatohepatitis-by-promoting-neutrophil-macrophage-crosstalk-via-the-induction-of-cxcr2
#10
Dewei Ye, Kangmin Yang, Shufei Zang, Zhuofeng Lin, Hau-Tak Chau, Yudong Wang, Jialiang Zhang, Junping Shi, Aimin Xu, Shaoqiang Lin, Yu Wang
No abstract text is available yet for this article.
January 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28058861/downregulation-of-transgelin-blocks-interleukin-8-utilization-and-suppresses-vasculogenic-mimicry-in-breast-cancer-cells
#11
Anastasia R Aikins, MiJung Kim, Bernardo Raymundo, Chan-Wha Kim
Vasculogenic mimicry (VM) is a non-classical mechanism recently described in many tumors, whereby cancer cells, rather than endothelial cells, form blood vessels. Transgelin is an actin-binding protein that has been implicated in multiple stages of cancer development. In this study, we investigated the role of transgelin in VM and assessed its effect on the expression of endothelial and angiogenesis-related genes during VM in MDA-MB-231 breast cancer cells. We confirmed the ability of MDA-MB-231 cells to undergo VM through a tube formation assay...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28013312/mycobacteria-manipulate-g-protein-coupled-receptors-to-increase-mucosal-rac1-expression-in-the-lungs
#12
Nader Alaridah, Nataliya Lutay, Erik Tenland, Anna Rönnholm, Oskar Hallgren, Manoj Puthia, Gunilla Westergren-Thorsson, Gabriela Godaly
Mycobacterium bovis bacille Calmette-Guérin (BCG) is currently the only approved vaccine against tuberculosis (TB). BCG mimics M. tuberculosis (Mtb) in its persistence in the body and is used as a benchmark to compare new vaccine candidates. BCG was originally designed for mucosal vaccination, but comprehensive knowledge about its interaction with epithelium is currently lacking. We used primary airway epithelial cells (AECs) and a murine model to investigate the initial events of mucosal BCG interactions...
December 24, 2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28011398/glycosaminoglycans-are-important-mediators-of-neutrophilic-inflammation-in-vivo
#13
Martha Gschwandtner, Elisabeth Strutzmann, Mauro M Teixeira, Hans J Anders, Maria Diedrichs-Möhring, Tanja Gerlza, Gerhild Wildner, Remo C Russo, Tiziana Adage, Andreas J Kungl
The pro-inflammatory chemokine interleukin-8 (CXCL8) exerts its function by establishing a chemotactic gradient in infected or damaged tissues to guide neutrophil granulocytes to the site of inflammation via its G protein-coupled receptors (GPCRs) CXCR1 and CXCR2 located on neutrophils. Endothelial glycosaminoglycans (GAGs) have been proposed to support the chemotactic gradient formation and thus the inflammatory response by presenting the chemokine to approaching leukocytes. In this study, we show that neutrophil transmigration in vitro can be reduced by adding soluble GAGs and that this process is specific with respect to the nature of the glycan...
December 20, 2016: Cytokine
https://www.readbyqxmd.com/read/28000523/cxcr2-inhibition-in-pancreatic-cancer-opportunities-for-immunotherapy
#14
Jennifer P Morton, Owen J Sansom
No abstract text is available yet for this article.
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27999173/rac-signal-adaptation-controls-neutrophil-mobilization-from-the-bone-marrow
#15
Carlo Cosimo Campa, Giulia Germena, Elisa Ciraolo, Francesca Copperi, Anna Sapienza, Irene Franco, Alessandra Ghigo, Annalisa Camporeale, Augusta Di Savino, Miriam Martini, Alessia Perino, Remco T A Megens, Angela R M Kurz, Christoph Scheiermann, Markus Sperandio, Andrea Gamba, Emilio Hirsch
Mobilization of neutrophils from the bone marrow determines neutrophil blood counts and thus is medically important. Balanced neutrophil mobilization from the bone marrow depends on the retention-promoting chemokine CXCL12 and its receptor CXCR4 and the egression-promoting chemokine CXCL2 and its receptor CXCR2. Both pathways activate the small guanosine triphosphatase Rac, leaving the role of this signaling event in neutrophil retention and egression ambiguous. On the assumption that active Rac determines persistent directional cell migration, we generated a mathematical model to link chemokine-mediated Rac modulation to neutrophil egression time...
December 20, 2016: Science Signaling
https://www.readbyqxmd.com/read/27995997/tiarp-attenuates-autoantibody-mediated-arthritis-via-the-suppression-of-neutrophil-migration-by-reducing-cxcl2-cxcr2-and-il-6-expression
#16
Asuka Inoue, Isao Matsumoto, Yuki Tanaka, Naoto Umeda, Chinatsu Takai, Hoshimi Kawaguchi, Hiroshi Ebe, Hiroto Yoshida, Yoshihiro Matsumoto, Seiji Segawa, Satoru Takahashi, Takayuki Sumida
TNFα-induced adipose-related protein (TIARP) is a six-transmembrane protein expressed on macrophages, neutrophils and synoviocytes. We reported recently that mice deficient in TIARP (TIARP(-/-)) spontaneously develop arthritis and are highly susceptible to collagen-induced arthritis (CIA) with enhanced interleukin (IL)-6 production. However, the effects of TIARP on neutrophils and fibroblast-like synoviocytes (FLS) have not been elucidated. We analyzed the roles of TIARP in K/BxN serum transfer model using TIARP(-/-) mice...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27974825/low-expression-of-cxcr1-2-on-neutrophils-predicts-poor-survival-in-patients-with-hepatitis-b-virus-related-acute-on-chronic-liver-failure
#17
Ruonan Xu, Chunmei Bao, Huihuang Huang, Fang Lin, Yue Yuan, Siyu Wang, Lei Jin, Tao Yang, Ming Shi, Zheng Zhang, Fu-Sheng Wang
Polymorphonuclear neutrophils (PMNs) and proinflammatory cytokines have been implicated in the pathogenesis of acute-on-chronic liver failure (ACLF). But the utility of CXC chemokine receptor expression on PMNs as a biomarker for prediction of disease severity is still uncertain. In this study, we investigated the dynamic expression of CXCR1 and CXCR2 on neutrophils, and found that patients with hepatitis B virus-related ACLF displayed low expression of CXCR1 and CXCR2 on peripheral neutrophils compared with healthy subjects and patients with chronic hepatitis B...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27966653/the-accessory-proteins-reep5-and-reep6-refine-cxcr1-mediated-cellular-responses-and-lung-cancer-progression
#18
Cho Rong Park, Dong-Joo You, Sumi Park, Sunam Mander, Da-Eun Jang, Su-Cheong Yeom, Seong-Hyun Oh, Curie Ahn, Sang Heon Lee, Jae Young Seong, Jong-Ik Hwang
Some G-protein-coupled receptors have been reported to require accessory proteins with specificity for proper functional expression. In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses. Although REEPs enhanced the expression of a subset of GPCRs, in the absence of REEP5 and REEP6, CXCR1 was expressed in the plasma membrane, but receptor internalization and intracellular clustering of β-arrestin2 following IL-8 treatment were impaired, suggesting that REEP5 and REEP6 might be involved in the ligand-stimulated endocytosis of CXCR1 rather than membrane expression, which resulted in strong cellular responses...
December 14, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27965576/functional-genomics-identifies-tis21-dependent-mechanisms-and-putative-cancer-drug-targets-underlying-medulloblastoma-shh-type-development
#19
Giulia Gentile, Manuela Ceccarelli, Laura Micheli, Felice Tirone, Sebastiano Cavallaro
We have recently generated a novel medulloblastoma (MB) mouse model with activation of the Shh pathway and lacking the MB suppressor Tis21 (Patched1(+/-)/Tis21(KO) ). Its main phenotype is a defect of migration of the cerebellar granule precursor cells (GCPs). By genomic analysis of GCPs in vivo, we identified as drug target and major responsible of this defect the down-regulation of the promigratory chemokine Cxcl3. Consequently, the GCPs remain longer in the cerebellum proliferative area, and the MB frequency is enhanced...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27965453/staphylococcus-aureus-leukocidin-luked-and-hiv-1-gp120-target-different-sequence-determinants-on-ccr5
#20
Kayan Tam, Megan Schultz, Tamara Reyes-Robles, Bénédicte Vanwalscappel, Joshua Horton, Francis Alonzo, Beili Wu, Nathaniel R Landau, Victor J Torres
: Leukocidin ED (LukED) is a bicomponent pore-forming toxin produced by Staphylococcus aureus that lyses host cells by targeting the chemokine receptors CC chemokine receptor type 5 (CCR5), CXCR1, CXCR2, and DARC. In addition to its role as a receptor for LukED, CCR5 is the major coreceptor for primary isolates of human immunodeficiency virus type 1 (HIV-1) and has been extensively studied. To compare how LukED and HIV-1 target CCR5, we analyzed their respective abilities to use CCR5/CCR2b chimeras to mediate cytotoxicity and virus entry...
December 13, 2016: MBio
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