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https://www.readbyqxmd.com/read/28642884/cxcl8b-and-cxcr2-regulate-neutrophil-migration-through-bloodstream-in-zebrafish
#1
Constanza Zuñiga-Traslaviña, Karina Bravo, Ariel E Reyes, Carmen G Feijóo
Neutrophils play an essential role during an inflammatory response, which is dependent on their rapid recruitment from the bone marrow to the vasculature. However, there is no information about the molecular signals that regulate neutrophil entry to circulation during an inflammatory process in humans. This is mainly due to the lack of a suitable model of study that contains similar set of molecules and that allows in vivo analyses. In this study, we used the zebrafish to assess the role of Cxcl8a, Cxcl8b, and Cxcr2 in neutrophil migration to blood circulation after injury...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28611093/danirixin-a-reversible-and-selective-antagonist-of-the-cxc-chemokine-receptor-2
#2
Jakob Busch-Petersen, Donald C Carpenter, Miriam Burman, James Foley, Gerald E Hunsberger, David J Kilian, Michael Salmon, Ruth J Mayer, John G Yonchuk, Ruth Tal-Singer
CXC chemokine receptor 2 (CXCR2) is a key receptor in the chemotaxis of neutrophils to sites of inflammation. The studies reported here describe the pharmacological characterization of danirixin, a CXCR2 antagonist in the diaryl urea chemical class. Danirixin has high affinity for CXCR2, with a negative log of the 50% inhibitory concentration (pIC50) of 7.9 for binding to Chinese hamster ovary cell (CHO)-expressed human CXCR2, and 78-fold selectivity over binding to CHO-expressed CXCR1. Danirixin is a competitive antagonist against CXCL8 in Ca2+ mobilization assays, with a Kb of 6...
June 13, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28596972/targets-of-neutrophil-influx-and-weaponry-therapeutic-opportunities-for-chronic-obstructive-airway-disease
#3
REVIEW
Carina Kärrman Mårdh, James Root, Mohib Uddin, Kristina Stenvall, Anna Malmgren, Kostas Karabelas, Matthew Thomas
Neutrophils are important effector cells of antimicrobial immunity in an acute inflammatory response, with a primary role in the clearance of extracellular pathogens. However, in respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD), there is excessive infiltration and activation of neutrophils, subsequent production of reactive oxygen species, and release of serine proteases, matrix metalloproteinases, and myeloperoxidase-resulting in collateral damage as the cells infiltrate into the tissue...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28587921/cxcl1-cxcr2-signaling-in-pathological-pain-role-in-peripheral-and-central-sensitization
#4
REVIEW
Rangel L Silva, Alexandre H Lopes, Rafaela M Guimarães, Thiago M Cunha
Pathological pain conditions can be triggered after peripheral nerve injury and/or inflammation. It is associated with plasticity of nociceptive pathway in which pain is prolonged even after healing of the injured tissue. Generally combinations of analgesic drugs are not sufficient to achieve selective palliation from chronic pain, besides causing a greater number of side effects. In order to identify novel alternatives for more effective treatments, it is necessary to clarify the underlying mechanisms of pathological pain...
June 3, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28575019/clinicopathologic-significance-of-the-cxcl1-cxcr2-axis-in-the-tumor-microenvironment-of-gastric-carcinoma
#5
Hiroaki Kasashima, Masakazu Yashiro, Hirohisa Nakamae, Go Masuda, Haruhito Kinoshita, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Takahiko Nakane, Masayuki Hino, Kosei Hirakawa, Masaichi Ohira
PURPOSE: It was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer. METHODS: The correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies...
2017: PloS One
https://www.readbyqxmd.com/read/28544630/synthesis-admet-properties-and-biological-evaluation-of-benzothiazole-compounds-targeting-cxcr2
#6
Wesam E Mehanna, Tiangong Lu, Bikash Debnath, Deena S Lasheen, Rabah A T Serya, Khaled A Abouzid, Nouri Neamati
Herein, we describe the synthesis and biological evaluation of a series of novel benzothiazoles based on a diaryl urea scaffold previously reported in some allosteric CXCR2 inhibitors. From a library of 41 new compounds, 17 showed significant inhibition of CXCR2 with IC50 less than 10 M and selectivity over CXCR4. Our ADMET simulations suggest favorable drug-like properties for the active compounds. Importantly, we developed a predictive model that can distinguish active from inactive compounds and will serve as a valuable tool to guide the design of optimized compounds to be evaluated in preclinical models...
May 23, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28539339/mif-2-d-dt-enhances-proximal-tubular-cell-regeneration-through-slpi-and-atf4-dependent-mechanisms
#7
Akinobu Ochi, Dong Chen, Wibke Schulte, Lin Leng, Nickolas Gilbert Moeckel, Marta Piecychna, Luisa Averdunk, Christian Stoppe, Richard Bucala, Gilbert W Moeckel
Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic actions that is produced by several organs and cell types. Depending on the target cell and the inflammatory context, MIF can engage its two component receptor complex CD74 and CD44, and the chemokine receptors CXCR2/4. MIF is constitutively expressed in renal proximal tubular cells, stored in intracellular preformed pools and is released at a low rate. Recently a second MIF-like protein (i.e. MIF-2/D-DT) has been characterized in mammals...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28538177/chemokine-signaling-and-the-regulation-of-bidirectional-leukocyte-migration-in-interstitial-tissues
#8
Davalyn Powell, Sebastien Tauzin, Laurel E Hind, Qing Deng, David J Beebe, Anna Huttenlocher
Motile cells navigate through complex tissue environments that include both attractive and repulsive cues. In response to tissue wounding, neutrophils, primary cells of the innate immune response, exhibit bidirectional migration that is orchestrated by chemokines and their receptors. Although progress has been made in identifying signals that mediate the recruitment phase, the mechanisms that regulate neutrophil reverse migration remain largely unknown. Here, we visualize bidirectional neutrophil migration to sterile wounds in zebrafish larvae and identify specific roles for the chemokine receptors Cxcr1 and Cxcr2 in neutrophil recruitment to sterile injury and infection...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28533661/macrophage-inflammatory-protein-2-as-mediator-of-inflammation-in-acute-liver-injury
#9
REVIEW
Chao-Chao Qin, Yan-Ning Liu, Ying Hu, Ying Yang, Zhi Chen
Macrophage inflammatory protein (MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand (CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activated-protein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2...
May 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28529998/complement-c5a-receptor-is-the-key-initiator-of-neutrophil-adhesion-igniting-immune-complex-induced-arthritis
#10
Yoshishige Miyabe, Chie Miyabe, Thomas T Murooka, Edward Y Kim, Gail A Newton, Nancy D Kim, Bodduluri Haribabu, Francis W Luscinskas, Thorsten R Mempel, Andrew D Luster
The deposition of immune complexes (IC) in tissues induces a "type III hypersensitivity" that results in tissue damage and underlies the pathogenesis of many autoimmune diseases. The neutrophil is the first immune cell recruited into sites of IC deposition and plays a critical role in shaping the overall tissue response. However, the mechanism by which IC initiate and propagate neutrophil infiltration into tissue is not known. Here, using intravital multiphoton joint imaging of IC-induced arthritis in live mice, we found that the complement C5a receptor (C5aR) was the key initiator of neutrophil adhesion on joint endothelium...
January 2017: Science Immunology
https://www.readbyqxmd.com/read/28514506/human-adipose-derived-mesenchymal-stem-cell-secreted-cxcl1-and-cxcl8-facilitate-breast-tumor-growth-by-promoting-angiogenesis
#11
Yuan Wang, Junli Liu, Qingyuan Jiang, Jie Deng, Fen Xu, Xiaolei Chen, Fuyi Cheng, Yujing Zhang, Yunqi Yao, Zhemin Xia, Xia Xu, Xiaolan Su, Meijuan Huang, Lei Dai, Yang Yang, Shuang Zhang, Dechao Yu, Robert Chunhua Zhao, Yuquan Wei, Hongxin Deng
Autologous adipose tissue or adipose tissue with additive adipose-derived mesenchymal stem cells (ADSCs) is used in the breast reconstruction of breast cancer patients who undergo mastectomy. ADSCs play an important role in the angiogenesis and adipogenesis, which make it much better than other materials. However, ADSCs may promote residual tumor cells to proliferate or metastasize, and the mechanism is still not fully understood. In our present study, we demonstrated that hADSCs could facilitate tumor cells growth after co-injection with MCF7 and ZR-75-30 breast cancer cells (BCCs) by promoting angiogenesis, but hADSCs showed limited effect on the growth of MDA-MB-231 BCCs...
May 17, 2017: Stem Cells
https://www.readbyqxmd.com/read/28484461/blockade-of-neutrophil-s-chemokine-receptors-cxcr1-2-abrogate-liver-damage-in-acute-on-chronic-liver-failure
#12
Arshi Khanam, Nirupma Trehanpati, Peggy Riese, Archana Rastogi, Carlos Alberto Guzman, Shiv Kumar Sarin
BACKGROUND: Neutrophils serve as critical players in the pathogenesis of liver diseases. Chemokine receptors CXCR1 and CXCR2 are required for neutrophil chemotaxis to the site of inflammation/injury and are crucial in hepatic inflammatory response. However, key mechanism of neutrophil-mediated liver injury in acute-on-chronic liver failure (ACLF) remains highly elusive; which could be targeted for the development of new therapeutic interventions. METHODS: To demonstrate the role of CXCR1/CXCR2-expressing neutrophils in hepatic injury, we investigated CXCR1/CXCR2 receptor expression in 17 hepatitis B virus-related ACLF patients in comparison to 42 chronic hepatitis B and 18 healthy controls...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28481874/a-positive-crosstalk-between-cxcr4-and-cxcr2-promotes-gastric-cancer-metastasis
#13
Z Xiang, Z-J Zhou, G-K Xia, X-H Zhang, Z-W Wei, J-T Zhu, J Yu, W Chen, Y He, R E Schwarz, R A Brekken, N Awasthi, C-H Zhang
The molecular mechanism underlying gastric cancer (GC) invasion and metastasis is still poorly understood. In this study, we tried to investigate the roles of CXCR4 and CXCR2 signalings in gastric cancer metastasis. A highly invasive gastric cancer cell model was established. Chemokines receptors were profiled to search for the accountable ones. Then the underlying molecular mechanism was investigated using both in vitro and in vivo techniques, and the clinical relevance of CXCR4 and CXCR2 expression was studied in gastric cancer samples...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28458362/elucidation-of-distinct-roles-of-guinea-pig-cxcr1-and-cxcr2-in-neutrophil-migration-toward-il-8-and-gro%C3%AE-by-specific-antibodies
#14
Kento Tanaka, Tomomi Yoshitomi, Kazuki Hirahara
Chemokine receptors CXCR1 and CXCR2 are conserved between guinea pigs and humans, but the distinct role of each receptor in chemotactic responses of neutrophils against chemokine ligands has not been elucidated due in part to the lack of specific inhibitors against these receptors in guinea pigs. In this study, we investigated the roles of guinea pig CXCR1 and CXCR2 on neutrophils in chemotactic responses to guinea pig interleukin (IL)-8 and growth-regulated oncogene (GRO)α by using specific inhibitory antibodies against these receptors...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28455419/cxcl1-is-critical-for-pre-metastatic-niche-formation-and-metastasis-in-colorectal-cancer
#15
Dingzhi Wang, Haiyan Sun, Jie Wei, Bo Cen, Raymond N DuBois
Emerging evidence suggests that the primary tumor influences the development of supportive metastatic microenvironments, referred to as pre-metastatic niches, in certain distant organs before arrival of metastatic cells.  However, the mechanisms underlying the contributions of the primary tumor to pre-metastatic niche formation are not fully understood.  Here we demonstrate that colorectal carcinoma cells secrete VEGF-A, which stimulates tumor-associated macrophages to produce CXCL1 in the primary tumor.  Elevation of CXCL1 in pre-metastatic liver tissue recruited CXCR2-positive myeloid-derived suppressor cells (MDSC) to form a pre-metastatic niche that ultimately promoted liver metastases...
April 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28450382/an-adaptive-signaling-network-in-melanoma-inflammatory-niches-confers-tolerance-to-mapk-signaling-inhibition
#16
Helen L Young, Emily J Rowling, Mattia Bugatti, Emanuele Giurisato, Nadia Luheshi, Imanol Arozarena, Juan-Carlos Acosta, Jivko Kamarashev, Dennie T Frederick, Zachary A Cooper, Alexandre Reuben, Jesus Gil, Keith T Flaherty, Jennifer A Wargo, William Vermi, Michael P Smith, Claudia Wellbrock, Adam Hurlstone
Mitogen-activated protein kinase (MAPK) pathway antagonists induce profound clinical responses in advanced cutaneous melanoma, but complete remissions are frustrated by the development of acquired resistance. Before resistance emerges, adaptive responses establish a mutation-independent drug tolerance. Antagonizing these adaptive responses could improve drug effects, thereby thwarting the emergence of acquired resistance. In this study, we reveal that inflammatory niches consisting of tumor-associated macrophages and fibroblasts contribute to treatment tolerance through a cytokine-signaling network that involves macrophage-derived IL-1β and fibroblast-derived CXCR2 ligands...
June 5, 2017: Journal of Experimental Medicine
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/28430080/generation-and-characterization-of-inhibitory-antibodies-specific-to-guinea-pig-cxcr1-and-cxcr2
#18
Kento Tanaka, Chigusa Yoshimura, Tetsuo Shiina, Tomoko Terauchi, Tomomi Yoshitomi, Kazuki Hirahara
CXCR1 and CXCR2 are chemokine receptors that have different selectivity of chemokine ligands, but the distinct role of each receptor is not clearly understood. This is due to the absence of specific inhibitors in guinea pigs, which are the appropriate species for investigation of CXCR1 and CXCR2 because of their functional similarity to humans. In this study, we generated and evaluated monoclonal antibodies that specifically bound to guinea pig CXCR1 (gpCXCR1) and guinea pig CXCR2 (gpCXCR2) for acquisition of specific inhibitors...
April 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28430079/monoclonal-antibody-abcr1-against-guinea-pig-cxcr1-and-monoclonal-antibody-abcr2-against-guinea-pig-cxcr2
#19
(no author information available yet)
No abstract text is available yet for this article.
April 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28429504/induced-pluripotent-stem-cells-reduce-neutrophil-chemotaxis-via-activating-grk2-in-endotoxin-induced-acute-lung-injury
#20
Vincent Yi-Fong Su, Shih-Hwa Chiou, Chi-Shiuan Lin, Wei-Chih Chen, Wen-Kuang Yu, Yen-Wen Chen, Cheng-Yu Chen, Kuang-Yao Yang
BACKGROUND AND OBJECTIVE: We investigated the effect of induced pluripotent stem cells (iPSCs) in moderating neutrophil chemotaxis in endotoxin-induced acute lung injury (ALI). METHODS: Male C57BL/6 mice at 8-12 weeks of age were studied. Murine iPSCs were delivered through the tail veins of mice 4 h after intratracheal instillation of endotoxin. Lung histopathological findings, neutrophil counts in peripheral blood and bronchoalveolar lavage fluid (BALF), bone marrow (BM) cell distribution, expression of chemokine receptors and regulatory signalling pathways were analysed after 24 h...
April 21, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
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