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Elena Furio, Maria Jose García-Fuster, Josep Redon, Patrice Marques, Rebeca Ortega, Maria Jesus Sanz, Laura Piqueras
Mechanisms linking deep vein thrombosis (DVT) and subclinical atherosclerosis and risk of cardiovascular events are poorly understood. The aim of this study was to investigate the potential impact of CX3 CR1/CX3 CL1 axis in DVT-associated endothelial dysfunction. The study included 22 patients (age: 37.5 ± 8.2 years) with a history of idiopathic DVT and without known cardiovascular risk factors and 23 aged-matched control subjects (age: 34 ± 7.8 years). Flow cytometry was used to evaluate peripheral markers of platelet activation, leukocyte immunophenotypes and CX3 CR1/CX3 CL1 expression in both groups...
February 12, 2018: Thrombosis and Haemostasis
Soledad Urra, Martin C Fischer, José R Martínez, Loreto Véliz, Paulina Orellana, Antonieta Solar, Karen Bohmwald, Alexis Kalergis, Claudia Riedel, Alejandro H Corvalán, Juan C Roa, Rodrigo Fuentealba, C Joaquin Cáceres, Marcelo López-Lastra, Augusto León, Nicolás Droppelmann, Hernán E González
Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B...
January 5, 2018: Oncotarget
F A Tobolowsky, N Wada, O Martinez-Maza, L Magpantay, S L Koletar, F J Palella, T T Brown, J E Lake
INTRODUCTION: Lymphoid tissue fibrosis may contribute to incomplete immune reconstitution on antiretroviral therapy (ART) via local CD4+ T lymphocyte (CD4) depletion. Hyaluronic acid (HA) increases with fibrotic burden. CXCL4 concentrations increase in response to pro-fibrotic stimuli, but lower CXCL4 concentrations in HIV-infected individuals may reflect successful immune evasion by HIV. We investigated relationships between circulating HA and CXCL4 concentrations and immune reconstitution on ART in HIV-infected Multicenter AIDS Cohort Study participants...
2018: PloS One
Jian-Liang Li, Kai Li, Yuan Guo, Zheng Zhao, Li-Na Chen, Xiao-Hui Jiang, Yu-Jie Li, Ya Tu, Xiao-Jun Zheng
Cerebral malaria (CM), a severe neurological syndrome caused by Plasmodium falciparum infection, is a serious life-threatening disease with a high mortality. Survivors' persistent brain injury is manifested as long-term neurocognitive disorders. The main neuropathological feature of CM is the sequestration of parasited red blood cells (pRBCs) in cerebral microvessels. Other neuropathological features of CM include petechial hemorrhage in the brain parenchyma, annular hemorrhage, extensive brain endothelial cell activation, and focal endothelial cell injury and necrosis...
December 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Chi Chiu Mok, Samar Soliman, Ling Yin Ho, Fatma A Mohamed, Faten Ismail Mohamed, Chandra Mohan
BACKGROUND: The aim was to study urinary angiostatin, CXC chemokine ligand 4 (CXCL4) and vascular cell adhesion molecule-1 (VCAM-1) as biomarkers of renal disease in systemic lupus erythematosus (SLE). METHOD: Patients who fulfilled ≥ 4 American College of Rheumatology (ACR) criteria for SLE with active renal, active non-renal or inactive disease, and a group of healthy controls were studied. Urine samples were assayed for angiostatin, CXCL4 and VCAM-1 by ELISA, and normalized by creatinine...
January 11, 2018: Arthritis Research & Therapy
Marie Dominique Ah Kioon, Claudio Tripodo, David Fernandez, Kyriakos A Kirou, Robert F Spiera, Mary K Crow, Jessica K Gordon, Franck J Barrat
Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease...
January 10, 2018: Science Translational Medicine
Constantinos Bakogiannis, Marco Sachse, Kimon Stamatelopoulos, Konstantinos Stellos
Platelets are inflammatory anuclear cells with a well-established role in the development and manifestation of atherosclerosis. Activated platelets secrete a plethora of chemokines including CXCL4 or platelet factor 4 (PF4), CCL5, CXCL12 or stromal cell derived factor-1α (SDF-1α), CXCL16 and others, which initiate or promote local inflammatory processes at sites of vascular injury. These processes are mainly mediated by the recruitment of circulating haematopoietic stem cells, neutrophils, monocytes or lymphocytes on vascular wall...
December 1, 2017: Cytokine
Alsya J Affandi, Sandra C Silva-Cardoso, Samuel Garcia, Emmerik F A Leijten, Tessa S van Kempen, Wioleta Marut, Joel A G van Roon, Timothy R D J Radstake
CXCL4 regulates multiple facets of the immune response and is highly upregulated in various Th17-associated rheumatic diseases. However, whether CXCL4 plays a direct role in the induction of IL-17 production by human CD4+ T cells is currently unclear. Here, we demonstrated that CXCL4 induced human CD4+ T cells to secrete IL-17 that co-expressed IFN-γ and IL-22, and differentiated naïve CD4+ T cells to become Th17-cytokine producing cells. In a co-culture system of human CD4+ T cells with monocytes or myeloid dendritic cells, CXCL4 induced IL-17 production upon triggering by superantigen...
November 29, 2017: European Journal of Immunology
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
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...
March 2018: Immunology Letters
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
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
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...
November 17, 2017: ACS Chemical Biology
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
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
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
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
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
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
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
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