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https://www.readbyqxmd.com/read/29133955/chemokines-in-depression-in-health-and-in-inflammatory-illness-a-systematic-review-and-meta-analysis
#1
REVIEW
S P Leighton, L Nerurkar, R Krishnadas, C Johnman, G J Graham, J Cavanagh
Inflammatory illness is associated with depression. Preclinical work has shown that chemokines are linked with peripheral-central crosstalk and may be important in mediating depressive behaviours. We sought to establish what evidence exists that differences in blood or cerebrospinal fluid chemokine concentration discriminate between individuals with depression and those without. Following PRISMA guidelines, we systematically searched Embase, PsycINFO and Medline databases. We included participants with physical illness for subgroup analysis, and excluded participants with comorbid psychiatric diagnoses...
November 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29126878/dendritic-cells-in-systemic-sclerosis-advances-from-human-and-mice-studies
#2
REVIEW
Alsya J Affandi, Tiago Carvalheiro, Timothy R D J Radstake, Wioleta Marut
Systemic sclerosis (SSc) is a complex heterogeneous fibrotic autoimmune disease with an unknown exact etiology, and characterized by three hallmarks: fibrosis, vasculopathy, and immune dysfunction. Dendritic cells (DCs) are specialized cells in pathogen sensing with high potency of antigen presentation and capable of releasing mediators to shape the immune response. Altered DCs distributions and their impaired functions may account for their role in breaking the immune tolerance and driving inflammation in SSc, and the direct contribution of DCs in promoting endothelial dysfunction and fibrotic process has only begun to be understood...
November 7, 2017: Immunology Letters
https://www.readbyqxmd.com/read/29070980/components-in-plasma-derived-factor-viii-but-not-in-recombinant-factor-viii-downregulate-anti-inflammatory-surface-marker-cd163-in-human-macrophages-through-release-of-cxcl4-platelet-factor-4
#3
Anne Bertling, Martin F Brodde, Mayken Visser, Janina Treffon, Michelle Fennen, Anke C Fender, Reinhard Kelsch, Beate E Kehrel
BACKGROUND: Hemarthrosis, or bleeding into the joints, is a hallmark of hemophilia. Heme triggers oxidative stress, inflammation, and destruction of cartilage and bone. The haptoglobin-CD163-heme oxygenase-1 (HO-1) pathway circumvents heme toxicity through enzymatic degradation of heme and transcription of antioxidant genes. Plasma-derived factor concentrates contain many proteins that might impact on cellular pathways in joints, blood, and vessels. METHODS: Activation of platelets from healthy volunteers was assessed by flow cytometry analysis of fibrinogen binding and CD62P expression...
September 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28978662/fractalkine-induces-angiogenic-potential-in-cx3cr1-expressing-monocytes
#4
Youngrok Park, Joon Lee, Jae-Yong Kwak, Kyoungmi Noh, Eunjung Yim, Hyun-Kyung Kim, Young June Kim, Hal E Broxmeyer, Jeong-A Kim
We report the unique role of CX3CL1 (or fractalkine) on CD11b(+) myelomonocytic cells expressing CX3CR1, the only known receptor for CX3CL1, in promoting blood perfusion recovery. In a mouse ischemic hind-limb model, CD11b(+)CX3CR1(+) cells migrated to ischemic femoral muscles through CX3CL1-mediated chemotaxis. CD11b(+)CX3CR1(+) macrophages isolated from ischemic tissues [tissue (T)-CD11b(+)CX3CR1(+)] of muscle exert a proangiogenic effect through platelet factor-4 (CXCL4; PF-4) production. PF-4 does not promote angiogenesis by itself but, instead, increases VEGF-mediated angiogenesis...
October 4, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28945356/oligomerization-state-of-cxcl4-chemokines-regulates-g-protein-coupled-receptor-activation
#5
Ya-Ping Chen, Hsin-Li Wu, Kevin Boyé, Chen-Ya Pan, Yi-Chen Chen, Nadège Pujol, Chun-Wei Lin, Liang-Yuan Chiu, Clotilde Billottet, Isabel D Alves, Andreas Bikfalvi, Shih-Che Sue
CXCL4 chemokines have antiangiogenic properties, mediated by different mechanisms, including CXCR3 receptor activation. Chemokines have distinct oligomerization states that are correlated with their biological functions. CXCL4 exists as a stable tetramer under physiological conditions. It is unclear whether the oligomerization state impacts CXCL4-receptor interaction. We found that the CXCL4 tetramer is sensitive to pH and salt concentration. Residues Glu28 and Lys50 were important for tetramer formation, and the first β-strand and the C-terminal helix are critical for dimerization...
October 4, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28899579/cxcl4-induced-macrophages-in-human-atherosclerosis
#6
Gabriele Domschke, Christian A Gleissner
Atherosclerosis is considered an inflammatory disease of the arterial wall. Monocytes and monocyte-derived cells (most often termed macrophages) play an essential role in the formation of atherosclerotic lesions, as they take up lipids leading to subsequent foam cell formation accompanied by release of pro-inflammatory cytokines. Similarly, platelets have been discovered to represent an important cell type mediating inflammatory and immune processes in atherogenesis, mainly by secreting chemokines, which are stored in the platelets' alpha granules, upon platelet activation...
September 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28810552/anti-cxcl4-monoclonal-antibody-accelerates-telogen-to-anagen-transition-and-attenuates-apoptosis-of-the-hair-follicle-in-mice
#7
Wen Guan, Xiaolan Yu, Jingjing Li, Qing Deng, Yang Zhang, Jing Gao, Peng Xia, Yunsheng Yuan, Jin Gao, Liang Zhou, Wei Han, Yan Yu
Although hair loss or alopecia is a common disease, its exact mechanisms are not yet well understood. The present study investigated the hypothesis that the homeostatic regulation of genes during hair regeneration may participate in hair loss, based on the cyclicity of hair growth. A cluster of such genes was identified by an expression gene-array from the dorsal skin in a depilated mouse model, and CXCL4 was identified as a significantly regulated gene during the hair regeneration process. To elucidate the function of CXCL4 in hair growth, CXCL4 activity was blocked by the administration of an anti-CXCL4 monoclonal antibody (mAb)...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28782046/circulating-loxl2-levels-reflect-severity-of-intestinal-fibrosis-and-galt-cd4-t-lymphocyte-depletion-in-treated-hiv-infection
#8
Sophie Seang, Anoma Somasunderam, Maitreyee Nigalye, Ma Somsouk, Timoty W Schacker, Joyce L Sanchez, Peter W Hunt, Netanya S Utay, Jordan E Lake
BACKGROUND: Incomplete immune reconstitution may occur despite successful antiretroviral therapy (ART). Gut-associated lymphoid tissue (GALT) fibrosis may contribute via local CD4(+) T lymphocyte depletion, intestinal barrier disruption, microbial translocation, and immune activation. METHODS: In a cross-sectional analysis, we measured circulating fibrosis biomarker levels on cryopreserved plasma from adult HIV-infected (HIV+) SCOPE study participants on suppressive ART who also had fibrosis quantification on recto-sigmoid biopsies...
2017: Pathogens & Immunity
https://www.readbyqxmd.com/read/28730919/an-update-on-biomarker-discovery-and-use-in-systemic-sclerosis
#9
Takashi Matsushita, Kazuhiko Takehara
Systemic sclerosis (SSc) is an autoimmune disease characterized by excessive extracellular matrix deposition in the skin and internal organs. Three major abnormalities, autoimmunity, vasculopathy, and fibrosis, are considered to play important roles in the pathophysiology of SSc. SSc is a heterogeneous disease with clinical features, disease progress, therapeutic response, and prognosis. Therefore, identification of biomarkers, which can predict the course of the disease, is required for the progress of clinical practice...
July 25, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28599423/induction-of-cathepsin-b-by-the-cxcr3-chemokines-cxcl9-and-cxcl10-in-human-breast-cancer-cells
#10
Holger Bronger, Anne Karge, Tobias Dreyer, Daniela Zech, Sara Kraeft, Stefanie Avril, Marion Kiechle, Manfred Schmitt
Cathepsin B (CTSB) is a lysosomal cysteine protease that has been linked to the progression of breast cancer, for example by activation of other proteases and tumor-promoting cytokines, thereby supporting tumor invasion and metastasis. Previously, it was shown that CTSB cleaves and inactivates C-X-C motif chemokine receptor 3 (CXCR3) chemokines. As CXCR3 ligands have been demonstrated to induce proteases in cancer cells, the present study hypothesized that they may also affect CTSB in breast cancer cells. The results demonstrated that the human breast cancer tumor cell lines MCF-7 and MDA-MB-231 express the CXCR3 splice variants A and B and CTSB...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28559424/c-x-c-motif-chemokine-receptor-3-splice-variants-differentially-activate-beta-arrestins-to-regulate-downstream-signaling-pathways
#11
Jeffrey S Smith, Priya Alagesan, Nimit K Desai, Thomas F Pack, Jiao-Hui Wu, Asuka Inoue, Neil J Freedman, Sudarshan Rajagopal
Biased agonism, the ability of different ligands for the same receptor to selectively activate some signaling pathways while blocking others, is now an established paradigm for G protein-coupled receptor signaling. One group of receptors in which endogenous bias is critical is the chemokine system, consisting of over 50 ligands and 20 receptors that bind one another with significant promiscuity. We have previously demonstrated that ligands for the same receptor can cause biased signaling responses. The goal of this study was to identify mechanisms that could underlie biased signaling between different receptor splice variants...
August 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28544777/the-prognostic-significance-of-circulating-serum-amyloid-a-and-cxc-chemokine-ligand-4-in-osteosarcoma
#12
Ricardo J Flores, Aaron J Kelly, Yiting Li, Xiang Chen, Colin McGee, Mark Krailo, Donald A Barkauskas, John Hicks, Tsz-Kwong Man
BACKGROUND: Osteosarcoma (OS) is the most common pediatric bone cancer.  Despite advances in treatment regimens, the survival rate remains 60-70%.  There is an urgent need to identify prognostic biomarkers, so that targeted therapies can be developed to improve the outcome. PROCEDURE: Our laboratory has previously identified that circulating serum amyloid A (SAA) and CXC chemokine ligand 4 (CXCL4) are upregulated in patients with OS.  In this study, we tested if they could be used as prognostic biomarkers...
December 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28530237/anti-platelet-factor-4-polyanion-antibodies-mediate-a-new-mechanism-of-autoimmunity
#13
Thi-Huong Nguyen, Nikolay Medvedev, Mihaela Delcea, Andreas Greinacher
Antibodies recognizing complexes of the chemokine platelet factor 4 (PF4/CXCL4) and polyanions (P) opsonize PF4-coated bacteria hereby mediating bacterial host defense. A subset of these antibodies may activate platelets after binding to PF4/heparin complexes, causing the prothrombotic adverse drug reaction heparin-induced thrombocytopenia (HIT). In autoimmune-HIT, anti-PF4/P-antibodies activate platelets in the absence of heparin. Here we show that antibodies with binding forces of approximately 60-100 pN activate platelets in the presence of polyanions, while a subset of antibodies from autoimmune-HIT patients with binding forces ≥100 pN binds to PF4 alone in the absence of polyanions...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28515281/cxcl4-exposure-potentiates-tlr-driven-polarization-of-human-monocyte-derived-dendritic-cells-and-increases-stimulation-of-t-cells
#14
Sandra C Silva-Cardoso, Alsya J Affandi, Lotte Spel, Marta Cossu, Joel A G van Roon, Marianne Boes, Timothy R D J Radstake
Chemokines have been shown to play immune-modulatory functions unrelated to steering cell migration. CXCL4 is a chemokine abundantly produced by activated platelets and immune cells. Increased levels of circulating CXCL4 are associated with immune-mediated conditions, including systemic sclerosis. Considering the central role of dendritic cells (DCs) in immune activation, in this article we addressed the effect of CXCL4 on the phenotype and function of monocyte-derived DCs (moDCs). To this end, we compared innate and adaptive immune responses of moDCs with those that were differentiated in the presence of CXCL4...
July 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28476896/altered-cargo-proteins-of-human-plasma-endothelial-cell-derived-exosomes-in-atherosclerotic-cerebrovascular-disease
#15
Edward J Goetzl, Janice B Schwartz, Maja Mustapic, Iryna V Lobach, Richard Daneman, Erin L Abner, Gregory A Jicha
Plasma endothelial cell-derived exosomes (EDEs) and platelet-derived exosomes (PDEs) were precipitated and enriched separately by immunospecific absorption procedures for analyses of cargo proteins relevant to atherosclerosis. EDEs had usual exosome size and marker protein content, and significantly higher levels than PDEs of the endothelial proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase, whereas PDEs had significantly higher levels of platelet glycoprotein VI. EDE levels of VCAM-1, von Willebrand factor, platelet-derived growth factor (PDGF)-BB, angiopoietin-1, and lysyl oxidase-2 and the cerebrovascular-selective proteins glucose transporter 1, permeability-glycoprotein, and large neutral amino acid transporter 1 were significantly higher for 18 patients with cerebrovascular disease (CeVD) than for 18 age- and gender-matched control subjects...
August 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28454880/expression-of-negative-immune-regulatory-molecules-pro-inflammatory-chemokine-and-cytokines-in-immunopathology-of-ecm-developing-mice
#16
Ashwin V Khandare, Deepali Bobade, Mangesh Deval, Tushar Patil, Bhaskar Saha, D Prakash
The pathological events in human cerebral malaria are mimicked in the experimental cerebral malaria (ECM) in Plasmodium berghei ANKA (PBA)-infected C57BL/6 mice. Although previously implied in ECM, the kinetics of cytokines and chemokines expression-an essential functional feature for defining causality in ECM development-remained untested. Herein, we characterized the immunopathological changes and the expression of negative immune regulatory molecules, cytokines and chemokines through asymptomatic (3days after infection, 3dpi), symptomatic (5dpi) and ECM (7dpi) stages in PBA-infected C57BL/6 mice...
April 25, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28446981/role-of-cxc-group-chemokines-in-lung-cancer-development-and-progression
#17
Artjoms Spaks
BACKGROUND: Clinical and translational research on lung cancer patients undergoing surgical treatment can provide valuable scientific data and unique opportunity to study tumor microenvironment. CXC chemokines, which are members of a big family of cytokines, are undoubtedly involved in tumor growth regulation and metastasizing pathways. For better understanding of CXC chemokine involvement in the process of carcinogenesis we have studied the cohort of early stage non-small cell lung cancer patients undergoing surgery with curative intent...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28381538/chemokine-interactome-mapping-enables-tailored-intervention-in-acute-and-chronic-inflammation
#18
Philipp von Hundelshausen, Stijn M Agten, Veit Eckardt, Xavier Blanchet, Martin M Schmitt, Hans Ippel, Carlos Neideck, Kiril Bidzhekov, Julian Leberzammer, Kanin Wichapong, Alexander Faussner, Maik Drechsler, Jochen Grommes, Johanna P van Geffen, He Li, Almudena Ortega-Gomez, Remco T A Megens, Ronald Naumann, Ingrid Dijkgraaf, Gerry A F Nicolaes, Yvonne Döring, Oliver Soehnlein, Esther Lutgens, Johan W M Heemskerk, Rory R Koenen, Kevin H Mayo, Tilman M Hackeng, Christian Weber
Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers...
April 5, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28368308/chemokine-cxcl7-heterodimers-structural-insights-cxcr2-receptor-function-and-glycosaminoglycan-interactions
#19
Aaron J Brown, Prem Raj B Joseph, Kirti V Sawant, Krishna Rajarathnam
Chemokines mediate diverse fundamental biological processes, including combating infection. Multiple chemokines are expressed at the site of infection; thus chemokine synergy by heterodimer formation may play a role in determining function. Chemokine function involves interactions with G-protein-coupled receptors and sulfated glycosaminoglycans (GAG). However, very little is known regarding heterodimer structural features and receptor and GAG interactions. Solution nuclear magnetic resonance (NMR) and molecular dynamics characterization of platelet-derived chemokine CXCL7 heterodimerization with chemokines CXCL1, CXCL4, and CXCL8 indicated that packing interactions promote CXCL7-CXCL1 and CXCL7-CXCL4 heterodimers, and electrostatic repulsive interactions disfavor the CXCL7-CXCL8 heterodimer...
April 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28355185/myeloid-progenitor-cluster-formation-drives-emergency-and-leukaemic-myelopoiesis
#20
Aurélie Hérault, Mikhail Binnewies, Stephanie Leong, Fernando J Calero-Nieto, Si Yi Zhang, Yoon-A Kang, Xiaonan Wang, Eric M Pietras, S Haihua Chu, Keegan Barry-Holson, Scott Armstrong, Berthold Göttgens, Emmanuelle Passegué
Although many aspects of blood production are well understood, the spatial organization of myeloid differentiation in the bone marrow remains unknown. Here we use imaging to track granulocyte/macrophage progenitor (GMP) behaviour in mice during emergency and leukaemic myelopoiesis. In the steady state, we find individual GMPs scattered throughout the bone marrow. During regeneration, we observe expanding GMP patches forming defined GMP clusters, which, in turn, locally differentiate into granulocytes. The timed release of important bone marrow niche signals (SCF, IL-1β, G-CSF, TGFβ and CXCL4) and activation of an inducible Irf8 and β-catenin progenitor self-renewal network control the transient formation of regenerating GMP clusters...
April 6, 2017: Nature
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