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https://www.readbyqxmd.com/read/28341702/nras-destines-tumor-cells-to-the-lungs
#1
Anastasios D Giannou, Antonia Marazioti, Nikolaos I Kanellakis, Ioanna Giopanou, Ioannis Lilis, Dimitra E Zazara, Giannoula Ntaliarda, Danai Kati, Vasileios Armenis, Georgia A Giotopoulou, Anthi C Krontira, Marina Lianou, Theodora Agalioti, Malamati Vreka, Maria Papageorgopoulou, Sotirios Fouzas, Dimitrios Kardamakis, Ioannis Psallidas, Magda Spella, Georgios T Stathopoulos
The lungs are frequently affected by cancer metastasis. Although NRAS mutations have been associated with metastatic potential, their exact role in lung homing is incompletely understood. We cross-examined the genotype of various tumor cells with their ability for automatic pulmonary dissemination, modulated NRAS expression using RNA interference and NRAS overexpression, identified NRAS signaling partners by microarray, and validated them using Cxcr1- and Cxcr2-deficient mice. Mouse models of spontaneous lung metastasis revealed that mutant or overexpressed NRAS promotes lung colonization by regulating interleukin-8-related chemokine expression, thereby initiating interactions between tumor cells, the pulmonary vasculature, and myeloid cells...
March 24, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28333137/the-mtor-signal-regulates-myeloid-derived-suppressor-cells-differentiation-and-immunosuppressive-function-in-acute-kidney-injury
#2
Chao Zhang, Shuo Wang, Jiawei Li, Weitao Zhang, Long Zheng, Cheng Yang, Tongyu Zhu, Ruiming Rong
The mammalian target of rapamycin (mTOR) signal controls innate and adaptive immune response in multiple immunoregulatory contexts. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells of potent immunosuppressive capacity. In this study, we aimed to investigate the role of MDSCs in the protection of acute kidney injury (AKI) and the regulation of mTOR signal on MDSC's protective role in this context. In mice AKI model, rapamycin administration was associated with improved renal function, restored histological damage and decreased CD4(+) and CD8(+) T-cell infiltration in kidney tissue...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28331341/investigating-the-expression-effect-and-tumorigenic-pathway-of-padi2-in-tumors
#3
Wei Guo, Yabing Zheng, Bing Xu, Fang Ma, Chang Li, Xiaoqian Zhang, Yao Wang, Xiaotian Chang
BACKGROUND: Peptidylarginine deiminase (PAD) catalyzes the conversion of arginine residues to citrulline residues, termed citrullination. Recent studies have suggested that PAD isoform 2 (PADI2) plays an important role in tumors, although its tumorigenic effect and mechanism are largely unknown. MATERIALS AND METHODS: Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to investigate the expression level of PADI2 in various tumor tissues and patient blood samples, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28325862/reduced-pu-1-expression-underlies-aberrant-neutrophil-maturation-and-function-in-%C3%AE-thalassemia-mice-and-patients
#4
Panjaree Siwaponanan, Jurre Ynze Siegers, Razi Ghazali, Thian Ng, Bradley McColl, Garrett Zhen-Wei Ng, Philip Sutton, Nancy Wang, Isabelle Ooi, Chayada Thiengtavor, Suthat Fucharoen, Pornthip Chaichompoo, Saovaros Svasti, Odilia Louise Wijburg, Jim Vadolas
β-Thalassemia is associated with several abnormalities of the innate immune system. Neutrophils in particular are defective, predisposing patients to life-threatening bacterial infections. The molecular and cellular mechanisms involved in impaired neutrophil function remain incompletely defined. We used the Hbb(th3/+) β-thalassemia mouse and HbE/β-thalassemia patients to investigate dysregulated neutrophil activity. Mature neutrophils from Hbb(th3/+) mice displayed a significant reduction in chemotaxis, opsonophagocytosis and production of reactive oxygen species (ROS), closely mimicking the defective immune functions observed in β-thalassemia patients...
March 21, 2017: Blood
https://www.readbyqxmd.com/read/28319586/short-term-exercise-training-alters-leukocyte-chemokine-receptors-in-obese-adults
#5
Julianne C Barry, Svetlana Simtchouk, Cody Durrer, Mary E Jung, Jonathan P Little
Obesity is characterized by chronic low-grade inflammation driven by activation and tissue infiltration of circulating leukocytes. Although exercise has anti-inflammatory effects, the impact of exercise on mediators of leukocyte migration is unclear. PURPOSE: To determine the impact of high intensity interval training (HIIT) versus moderate intensity continuous training (MICT), in the absence of weight/fat loss, on circulating chemokines and leukocyte chemokine receptors. METHODS: Thirty-seven inactive obese adults were randomized to two weeks (10 sessions) of HIIT or MICT with fasting blood samples collected before and after training...
March 18, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28303009/resveratrol-sequentially-induces-replication-and-oxidative-stresses-to-drive-p53-cxcr2-mediated-cellular-senescence-in-cancer-cells
#6
Boxuan Li, Dong Hou, Haiyang Guo, Haibin Zhou, Shouji Zhang, Xiuhua Xu, Qiao Liu, Xiyu Zhang, Yongxin Zou, Yaoqin Gong, Changshun Shao
Resveratrol (RSV) acts either as an antioxidant or a pro-oxidant depending on contexts. RSV-treated cancer cells may experience replication stress that can lead to cellular senescence or apoptosis. While both oxidative and replication stresses may mediate the anti-proliferation effect of RSV, to what extent each contributes to the impaired proliferation in response to RSV remains uncharacterized. We here report the study of the roles of replication and oxidative stresses in mediating cellular senescence in cancer cells treated with RSV...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28294319/grpr-antagonist-protects-from-drug-induced-liver-injury-by-impairing-neutrophil-chemotaxis-and-motility
#7
Rafael S Czepielewski, Natália Jaeger, Pedro E Marques, Maísa M Antunes, Maurício M Rigo, Débora M Alvarenga, Rafaela V Pereira, Rodrigo D da Silva, Tiago G Lopes, Vinícius D da Silva, Bárbara N Porto, Gustavo B Menezes, Cristina Bonorino
Drug-induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXCR2 ligands (IL-8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life threatening tissue damage that ensues. A GRPR (gastrin-releasing peptide receptor) antagonist impairs IL-8-induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen-induced ALF, neutrophil migration and mechanisms underlying this phenomenon...
March 10, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28277406/comparable-neutrophil-responses-for-arm-and-intensity-matched-leg-exercise
#8
Christof A Leicht, Victoria L Goosey-Tolfrey, Nicolette C Bishop
INTRODUCTION: Arm exercise is performed at lower absolute intensities than lower body exercise. This may impact on intensity dependent neutrophil responses and it is unknown whether individuals restricted to arm exercise experience the same changes in the neutrophil response as found for lower body exercise. Therefore, we aimed to investigate the importance of exercise modality and relative exercise intensity on the neutrophil response. METHODS: Twelve moderately trained males performed three 45-min constant load exercise trials following determination of peak oxygen uptake for arm exercise (V[Combining Dot Above]O2peak arms) and cycling (V[Combining Dot Above]O2peak legs): (1) arm cranking exercise at 60%V[Combining Dot Above]O2peak arms; (2) moderate cycling at 60%V[Combining Dot Above]O2peak legs; and (3) easy cycling at 60%V[Combining Dot Above]O2peak arms...
March 8, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28277189/cxcl5-plays-a-promoting-role-in-osteosarcoma-cell-migration-and-invasion-in-autocrine-and-paracrine-dependent-manners
#9
Hongsheng Dang, Wuzhou Wu, Bo Wang, Cao Cui, Juwei Niu, Jie Chen, Ziqiu Chen, Yi Liu
CXCL5, a CXC-type chemokine, is an important attractant for granulocytic immune cells by binding to its receptor CXCR2. Recently, CXCL5/CXCR2 has been found to play an oncogenic role in many human cancers. However, the exact role of CXCL5 in osteosarcoma cell migration and invasion has not been revealed. Here we found that the protein expression of CXCL5 was significantly increased in osteosarcoma tissues compared with that in matched adjacent nontumor tissues. Moreover, the expression of CXCL5 was significantly associated with advanced clinical stage and metastasis...
January 26, 2017: Oncology Research
https://www.readbyqxmd.com/read/28245630/structural-basis-of-native-cxcl7-monomer-binding-to-cxcr2-receptor-n-domain-and-glycosaminoglycan-heparin
#10
Aaron J Brown, Krishna Mohan Sepuru, Krishna Rajarathnam
CXCL7, a chemokine highly expressed in platelets, orchestrates neutrophil recruitment during thrombosis and related pathophysiological processes by interacting with CXCR2 receptor and sulfated glycosaminoglycans (GAG). CXCL7 exists as monomers and dimers, and dimerization (~50 μM) and CXCR2 binding (~10 nM) constants indicate that CXCL7 is a potent agonist as a monomer. Currently, nothing is known regarding the structural basis by which receptor and GAG interactions mediate CXCL7 function. Using solution nuclear magnetic resonance (NMR) spectroscopy, we characterized the binding of CXCL7 monomer to the CXCR2 N-terminal domain (CXCR2Nd) that constitutes a critical docking site and to GAG heparin...
February 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28243237/critical-role-of-myeloid-derived-suppressor-cells-in-tumor-induced-liver-immune-suppression-through-inhibition-of-nkt-cell-function
#11
Hongru Zhang, Zheng Li, Li Wang, Gaofei Tian, Jun Tian, Zishan Yang, Guangchao Cao, Hong Zhou, Liqing Zhao, Zhenzhou Wu, Zhinan Yin
Metastasis followed by the tumor development is the primary cause of death for cancer patients. However, the underlying molecular mechanisms of how the growth of tumor resulted in the immune suppression, especially at the blood-enriched organ such as liver, were largely unknown. In this report, we studied the liver immune response of tumor-bearing (TB) mice using concanavalin A (Con A)-induced hepatitis model. We demonstrated that TB mice displayed an immune suppression phenotype, with attenuated alanine aminotransferase levels and liver damage upon Con A treatment...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28237625/selective-sensitization-of-human-neutrophils-to-lukgh-mediated-cytotoxicity-by-staphylococcus-aureus-and-il-8
#12
Philipp Janesch, Harald Rouha, Susanne Weber, Stefan Malafa, Karin Gross, Barbara Maierhofer, Adriana Badarau, Zehra C Visram, Lukas Stulik, Eszter Nagy
OBJECTIVES: Staphylococcus aureus produces up to five bi-component leukocidins - LukSF-PV, gamma-hemolysins AB and CB, LukGH (LukAB) and LukED - to evade innate immunity by lysing phagocytic cells. Species specificity of these leukocidins limits the relevance of animal models, therefore we assessed their individual contribution using human neutrophils. METHODS: Human polymorphonuclear leukocytes (PMNs) were activated with stimuli relevant during bacterial infections and sensitivity to recombinant leukocidins was measured in cell-viability assays...
February 22, 2017: Journal of Infection
https://www.readbyqxmd.com/read/28230162/n-acetylated-proline-glycine-proline-accelerates-cutaneous-wound-healing-and-neovascularization-by-human-endothelial-progenitor-cells
#13
Yang Woo Kwon, Soon Chul Heo, Tae Wook Lee, Gyu Tae Park, Jung Won Yoon, Il Ho Jang, Seung-Chul Kim, Hyun-Chang Ko, Youngjae Ryu, Hyeona Kang, Chang Man Ha, Sang Chul Lee, Jae Ho Kim
Human endothelial progenitor cells (hEPCs) are promising therapeutic resources for wound repair through stimulating neovascularization. However, the hEPCs-based cell therapy has been hampered by poor engraftment of transplanted cells. In this study, we explored the effects of N-acetylated Proline-Glycine-Proline (Ac-PGP), a degradation product of collagen, on hEPC-mediated cutaneous wound healing and neovascularization. Treatment of hEPCs with Ac-PGP increased migration, proliferation, and tube-forming activity of hEPCs in vitro...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28222329/inflammatory-chemokines-and-their-receptors-in-human-visceral-leishmaniasis-gene-expression-profile-in-peripheral-blood-splenic-cellular-sources-and-their-impact-on-trafficking-of-inflammatory-cells
#14
Neetu Singh, Shyam Sundar
Chemokines play an important role in determining cellular composition at inflammatory sites, and as such, influence disease outcome. In this study, we investigated the expression profile and splenic cellular source of various inflammatory chemokines and their receptors in human visceral leishmaniasis (VL). The expression of chemokines or their receptors was measured at the gene and protein level by employing real time qPCR and a cytometric bead array assay, respectively. In addition, the cellular source of chemokines and their receptors in the spleen was identified employing gene expression analyses in sequentially selected cell subsets...
February 18, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28214673/duffy-antigen-receptor-for-chemokines-darc-expressing-in-cancer-cells-inhibits-tumor-progression-by-suppressing-cxcr2-signaling-in-human-pancreatic-ductal-adenocarcinoma
#15
Shintaro Maeda, Satoshi Kuboki, Hiroyuki Nojima, Hiroaki Shimizu, Hideyuki Yoshitomi, Katsunori Furukawa, Masaru Miyazaki, Masayuki Ohtsuka
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Chemokines play important roles in the progression of many malignancies; however, the role of chemokine receptor expression in clinical cases of PDAC is unclear. Moreover, little is known about DARC, a decoy receptor of CXC chemokines, in the regulation of tumor progression. METHODS: Functions of chemokine receptors were evaluated using surgical specimens collected from PDAC patients, and PDAC cell lines...
February 16, 2017: Cytokine
https://www.readbyqxmd.com/read/28205614/cxcr2-deficient-mice-display-macrophage-dependent-exaggerated-acute-inflammatory-responses
#16
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
#17
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
#18
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...
April 1, 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
#19
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
#20
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
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