Search results for " CXC"
showing 10 items of 84 documents
Regulatory T cells selectively preserve immune privilege of self-antigens during viral central nervous system infection.
2012
Abstract Regulatory T cells (Tregs) are important for the attenuation of immune reactions. During viral CNS infections, however, an indiscriminate maintenance of CNS immune privilege through Treg-mediated negative regulation could prevent autoimmune sequelae but impair the control of viral replication. We analyzed in this study the impact of Tregs on the development of acute viral encephalomyelitis, T cell-mediated antiviral protection, and prevention of CNS autoimmunity following intranasal infection with the gliatropic mouse hepatitis virus strain A59. To assess the contribution of Tregs in vivo, we specifically depleted CD4+Foxp3+ T cells in a diphtheria toxin-dependent manner. We found …
Novel therapeutic targets in esophageal cancer: impact of chemokine receptor CXCR4
2007
Ines Gockel†, Carl C Schimanski, Markus Moehler & Theodor Junginger †Author for correspondence Johannes GutenbergUniversity of Mainz, Department of General and Abdominal Surgery, Langenbeckstr. 1, 55131 Mainz, Germany Tel.: +49 6131 177 291; Fax: +49 6131 176 630; gockel@ach.klinik.unimainz.de ‘The interaction between esophageal cancer-expressed CXCR4 and SDF-1α may have a key role in directing malignant cells to ‘homing’ organs ... thus, this mechanism may account for metastasis.’
Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system.
2014
The proper functioning of the dopaminergic system requires the coordinated formation of projections extending from dopaminergic neurons in the substantia nigra (SN), ventral tegmental area (VTA) and retrorubral field to a wide array of forebrain targets including the striatum, nucleus accumbens and prefrontal cortex. The mechanisms controlling the assembly of these distinct dopaminergic cell clusters are not well understood. Here, we have investigated in detail the migratory behavior of dopaminergic neurons giving rise to either the SN or the medial VTA using genetic inducible fate mapping, ultramicroscopy, time-lapse imaging, slice culture and analysis of mouse mutants. We demonstrate that…
Endothelial cells and normal breast epithelial cells enhance invasion of breast carcinoma cells by CXCR-4-dependent up-regulation of urokinase-type p…
2008
Here we show the increase of invasion of three breast cancer cell lines (8701-BC, MDA-MB-231 and SKBR3) upon long-term co-incubation with culture medium of normal microvascular endothelial cells (MVEC) and normal breast epithelial cells (HB2). The enhancement of invasion relied on the interaction of microvascular endothelial cell and normal breast epithelial cell CXCL12 (SDF1) chemokine, whose expression by breast cancer cells was very low, with the cognate CXCR4 receptor of malignant cells, which resulted in over-expression of the urokinase-type plasminogen activator receptor (uPAR) on their surfaces. uPAR over-expression, showed by RT-PCR and Western blotting, was paralleled by increased …
Chemokine receptor CXCR4-prognostic factor for gastrointestinal tumors
2008
To review the implication of CXCR4 for gastrointestinal cancer, a "Pubmed" analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers. Search terms applied were "cancer, malignoma, esophageal, gastric, colon, colorectal, hepatic, pancreatic, CXCR4, SDF-1alpha, and SDF-1beta". CXCR4 expression correlated with dissemination of diverse gastrointestinal malignomas. The CXCR4 ligand SDF-1alpha might act as "chemorepellent" while SDF-1beta might act as "chemorepellent" for CTLs, inducing tumor rejection. The paracrine expression of SDF-1alpha was furthermore closely associated with neoangiogenesis. CXCR4 and its ligands influence the disseminat…
PAR1 signaling regulates the retention and recruitment of EPCR-expressing bone marrow hematopoietic stem cells
2015
Retention of long-term repopulating hematopoietic stem cells (LT-HSCs) in the bone marrow is essential for hematopoiesis and for protection from myelotoxic injury. We report that signaling cascades that are traditionally viewed as coagulation related also control retention of endothelial protein C receptor-positive (EPCR(+)) LT-HSCs in the bone marrow and their recruitment to the blood via two pathways mediated by protease activated receptor 1 (PAR1). Thrombin-PAR1 signaling induces nitric oxide (NO) production, leading to EPCR shedding mediated by tumor necrosis factor-α-converting enzyme (TACE), enhanced CXCL12-CXCR4-induced motility and rapid stem and progenitor cell mobilization. Conver…
C-X-C Motif Chemokine Receptor 4 Blockade Promotes Tissue Repair After Myocardial Infarction by Enhancing Regulatory T Cell Mobilization and Immune-R…
2019
Background: Acute myocardial infarction (MI) elicits an inflammatory response that drives tissue repair and adverse cardiac remodeling. Inflammatory cell trafficking after MI is controlled by C-X-C motif chemokine ligand 12 (CXCL12) and its receptor, C-X-C motif chemokine receptor 4 (CXCR4). CXCR4 antagonists mobilize inflammatory cells and promote infarct repair, but the cellular mechanisms are unclear. Methods: We investigated the therapeutic potential and mode of action of the peptidic macrocycle CXCR4 antagonist POL5551 in mice with reperfused MI. We applied cell depletion and adoptive transfer strategies using lymphocyte-deficient Rag1 knockout mice; DEREG mice, which express a diphth…
Establishment of an HIV cell-cell fusion assay by using two genetically modified HeLa cell lines and reporter gene.
2003
Infection of human cells with the human immunodeficiency virus type I (HIV-1) can be mimicked by a fusion process between cells expressing the HIV envelope protein (Env) and cells expressing both human CD4 together with the appropriate human chemokine receptors. In this study, a T-tropic HIV cell-cell fusion assay was established that utilized CD4, human CXCR4 and HIV NL4-3 gp160 as fusion components and a T7 polymerase-activated luciferase as a reporter system. The HeLa T4 cells used, expressed CD4 and CXCR4, and the applied HeLa KS386 cells expressed HIV NL4-3 gp160. By combining HeLa T4 cells with HeLa KS386 cells, an approximately about 100- to 300-fold increase in luciferase activity c…
IFN-gamma-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations
2007
BACKGROUND: Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations. OBJECTIVE: We assessed which inflammatory mediators were released from bronchial epithelial cells (BECs) after infection with rhinovirus and then determined whether they were also present in subjects with acute virus-induced asthma, with the aim to identify a biomarker or biomarkers for acute virus-induced asthma. METHODS: BECs were obtained from bronchial brushings of steroid-naive asthmatic subjects and healthy nonatopic control subjects. Cells were infected with rhinovirus 16. Inflammatory mediators were measured by means of flow cytometry with a cytometric bead array. Subjects with acute a…
3′-Demethyldihydromaldoxin and dihydromaldoxin, two anti-inflammtory diaryl ethers from a Steganospora species
2012
CXCL10 (IP-10) is a highly inducible chemoattractant, which contributes to the recruitment of inflammatory cells such as macrophages and T-lymphocytes and thereby has important roles in chronic inflammatory conditions. In a search for new inhibitors of CXCL10 expression in MonoMac6 (MM6) cells, the new diaryl ether 3'-demethyldihydromaldoxin (1) along with the known compound dihydromaldoxin (2), were isolated from fermentations of a Steganospora species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy and mass spectrometry. Compounds (1) and (2) inhibited lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced CXCL10 promoter activ…