The Experts below are selected from a list of 243534 Experts worldwide ranked by ideXlab platform
Robert M. Strieter - One of the best experts on this subject based on the ideXlab platform.
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Chemokines in the Lung - Chemokines in the lung
2003Co-Authors: Robert M. Strieter, Steven L. Kunkel, Theodore J. StandifordAbstract:Chemokines ligands Chemokine receptors Chemokine signal transduction stat 4 and stat 6 signalling and Chemokine expression the role of Chemokines in lymphocyte trafficking to secondary lymph nodes applicable to the lung the use of geneticapproaches to assess Chemokine biology Chemokines in asthma Chemokines in chronic bronchitis Chemokines in cystic fibrosis Chemokines in infectious diseases of the lung Chemokines and AIDS Chemokines in acute lung injury Chemokines in granulomatousdisease of the lung Chemokines in pulmonary fibrosis Chemokines in lung transplantation Chemokines in lung cancer Chemokines in pleural disorders.
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Potential role for Duffy antigen Chemokine-binding protein in angiogenesis and maintenance of homeostasis in response to stress
Journal of Leukocyte Biology, 2002Co-Authors: Jianguo Du, Yingchun Yu, Theresa S. Chen, Hua Liu, Thomas O Daniel, Lillian B Nanney, Linda W. Horton, Jing Luan, Stephen C. Peiper, Robert M. StrieterAbstract:CXC Chemokines, which induce angiogenesis, have glutamine-leucine-arginine amino acid residues (ELR motif) in the amino terminus and bind CXCR2 and the Duffy antigen Chemokine-binding protein. Duffy, a seven transmembrane protein that binds CXC and CC Chemokines, has not been shown to couple to trimeric G proteins or to transduce intracellular signals, although it is highly expressed on red blood cells, endothelial cells undergoing neovascularization, and neuronal cells. The binding of Chemokines by Duffy could modulate Chemokine responses positively or negatively. Positive regulation could come through the presentation of Chemokine to functional receptors, and negative regulation could come through Duffy competition with functional Chemokine receptors for Chemokine binding, thus serving as a decoy receptor. To determine whether Duffy has a role in angiogenesis and/or maintenance of homeostasis, we developed transgenic mice expressing mDuffy under the control of the preproendothelin promoter/enhancer (PPEP), which directs expression of the transgene to the endothelium. Two PPEP-mDuffy-transgenic founders were identified, and expression of the transgene in the endothelium was verified by Northern blot, RT-PCR, and immunostaining of tissues. The phenotype of the mice carrying the transgene appeared normal by all visual parameters. However, careful comparison of transgenic and nontransgenic mice revealed two phenotypic differences: mDuffy-transgenic mice exhibited a diminished angiogenic response to MIP-2 in the corneal micropocket assay, and mDuffy-transgenic mice exhibited enhanced hepatocellular toxicity and necrosis as compared with nontransgenic littermates in response to overdose of acetaminophen (APAP; 400 mg/kg body weight). Morover, APAP treatment was lethal in 50% of the mDuffy-transgenic mice 24 h post challenge, and 100% of the nontransgenic litter-mates survived this treatment at the 24 h time point. Our data suggest that enhanced expression of mDuffy on endothelial cells can lead to impaired angiogenic response to Chemokines and impaired maintenance of homeostasis in response to toxic stresses.
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expression of specific Chemokines and Chemokine receptors in the central nervous system of multiple sclerosis patients
Journal of Clinical Investigation, 1999Co-Authors: Torben Lykke Sorensen, Marie Tani, Jakob Sondergaard Jensen, Virginia Pierce, Claudia F Lucchinetti, Virginia A Folcik, James B Rottman, Finn Sellebjerg, Robert M. StrieterAbstract:Chemokines direct tissue invasion by specific leukocyte populations. Thus, Chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether specific Chemokines were expressed in the CNS during acute demyelinating events by analyzing cerebrospinal fluid (CSF), whose composition reflects the CNS extracellular space. During MS attacks, we found elevated CSF levels of three Chemokines that act toward T cells and mononuclear phagocytes: interferon-γ–inducible protein of 10 kDa (IP-10); monokine induced by interferon-γ (Mig); and regulated on activation, normal T-cell expressed and secreted (RANTES). We then investigated whether specific Chemokine receptors were expressed by infiltrating cells in demyelinating MS brain lesions and in CSF. CXCR3, an IP-10/Mig receptor, was expressed on lymphocytic cells in virtually every perivascular inflammatory infiltrate in active MS lesions. CCR5, a RANTES receptor, was detected on lymphocytic cells, macrophages, and microglia in actively demyelinating MS brain lesions. Compared with circulating T cells, CSF T cells were significantly enriched for cells expressing CXCR3 or CCR5. Our results imply pathogenic roles for specific Chemokine–Chemokine receptor interactions in MS and suggest new molecular targets for therapeutic intervention.
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cell to cell and cell to matrix interactions mediate Chemokine expression an important component of the inflammatory lesion
Journal of Leukocyte Biology, 1997Co-Authors: Robert E Smith, Robert M. Strieter, Cory M. Hogaboam, N W Lukacs, S L KunkelAbstract:: Although many studies have characterized soluble factors that stimulate or inhibit Chemokine secretion, in this review we focus on the event of cellular adhesion as a novel mechanism for stimulating Chemokine expression. Recent work has demonstrated Chemokine expression following cell-to-cell and cell-to-matrix adhesion. The specificity of this finding was demonstrated utilizing various techniques that illustrate that adhesion, and not a soluble stimulus, is in some cases responsible for initiating or augmenting Chemokine expression. For example, co-cultures of peripheral blood monocytes and endothelial cells secreted elevated levels of IL-8 and MCP-1 compared with either cell type alone. When co-cultured in transwells, this effect was significantly attenuated. In other experiments, neutralizing monoclonal antibodies to various adhesion molecules inhibited Chemokine expression. The effects of adhesion were not limited to leukocytes. Both immune and non-immune cell types were evaluated as potential sources of adhesion-mediated Chemokine expression. Not suprisingly, expression of some Chemokines was associated with adhesion, whereas others were not, supporting the notion that adhesion differentially signals Chemokine secretion during the inflammatory response. We hypothesize that as a recruited leukocyte encounters different adhesion substrates such as endothelial cells, basement membrane, extracellular matrix, and fibroblasts, the expression of Chemokines from both the leukocyte and the substrate may be initiated, inhibited, or augmented. Careful characterization of the contribution of adhesion to regulation of Chemokine expression will provide insight into the pathogenesis of many human diseases where Chemokines have a central role.
Torben Lykke Sorensen - One of the best experts on this subject based on the ideXlab platform.
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expression of specific Chemokines and Chemokine receptors in the central nervous system of multiple sclerosis patients
Journal of Clinical Investigation, 1999Co-Authors: Torben Lykke Sorensen, Marie Tani, Jakob Sondergaard Jensen, Virginia Pierce, Claudia F Lucchinetti, Virginia A Folcik, James B Rottman, Finn Sellebjerg, Robert M. StrieterAbstract:Chemokines direct tissue invasion by specific leukocyte populations. Thus, Chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether specific Chemokines were expressed in the CNS during acute demyelinating events by analyzing cerebrospinal fluid (CSF), whose composition reflects the CNS extracellular space. During MS attacks, we found elevated CSF levels of three Chemokines that act toward T cells and mononuclear phagocytes: interferon-γ–inducible protein of 10 kDa (IP-10); monokine induced by interferon-γ (Mig); and regulated on activation, normal T-cell expressed and secreted (RANTES). We then investigated whether specific Chemokine receptors were expressed by infiltrating cells in demyelinating MS brain lesions and in CSF. CXCR3, an IP-10/Mig receptor, was expressed on lymphocytic cells in virtually every perivascular inflammatory infiltrate in active MS lesions. CCR5, a RANTES receptor, was detected on lymphocytic cells, macrophages, and microglia in actively demyelinating MS brain lesions. Compared with circulating T cells, CSF T cells were significantly enriched for cells expressing CXCR3 or CCR5. Our results imply pathogenic roles for specific Chemokine–Chemokine receptor interactions in MS and suggest new molecular targets for therapeutic intervention.
Augustin Fliche - One of the best experts on this subject based on the ideXlab platform.
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Chemokines and Chemokine receptors: new insights into cancer- related inflammation
Trends in Molecular Medicine, 2011Co-Authors: Site Saint, Eloi Bâtiment, Augustin FlicheAbstract:Chemokines are involved in cellular interactions and tropism in situations frequently associated with inflammation. Recently, the importance of Chemokines and Chemokine receptors in inflammation associated with carcinogenesis has been highlighted. Increasing evidence suggests that Chemokines are produced by tumor cells and also by cells of the tumor microenvironment including cancer- associated fibroblasts, mesenchymal stem cells, endothelial cells, tumor-associated macrophages and more recently tumor-associated neutrophils. In addition to having effects on tumor cell proliferation, angiogenesis and metastasis, Chemokines also appear to modulate senescence and cell survival. Here, we review recent progress on the roles of Chemokines and Chemokine receptors in cancer-related inflammation, and we discuss the mechanisms underlying Chemokine action in cancer that might facilitate the development of novel therapies in the future.
Robert C. Gallo - One of the best experts on this subject based on the ideXlab platform.
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Chemokine Receptors and Chemokines in HIV Infection
Journal of Clinical Immunology, 1998Co-Authors: Alfredo Garzino-demo, Anthony L. Devico, Robert C. GalloAbstract:Suppression of HIV by Chemokines represents a special case in virology and immunology where soluble molecules other than antibodies inhibit infection by a specific virus. The basis for this inhibition is that HIV has evolved to use certain Chemokine receptors as “coreceptors” for entry into host cells. Human genotypes that reduce or prevent coreceptor expression are strongly associated with protection against infection and slower disease progression. We suggest that local production of certain Chemokines can produce a similar modulation of coreceptor expression, and mounting evidence indicates that Chemokine release is a major determinant of protection from HIV infection. Here we review this evidence and explore future avenues for investigating the role of Chemokines in controlling HIV infection.
Ann Richmond - One of the best experts on this subject based on the ideXlab platform.
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Chemokines and Chemokine receptors: new insights into cancer-related inflammation
Trends in Molecular Medicine, 2010Co-Authors: Gwendal Lazennec, Ann RichmondAbstract:Chemokines are involved in cellular interactions and tropism in situations frequently associated with inflammation. Recently, the importance of Chemokines and Chemokine receptors in inflammation associated with carcinogenesis has been highlighted. Increasing evidence suggests that Chemokines are produced by tumor cells as well as by cells of the tumor microenvironment including cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, tumor-associated macrophages (TAMs) and more recently tumor-associated neutrophils (TANs). In addition to affecting tumor cell proliferation, angiogenesis and metastasis, Chemokines also seem to modulate senescence and cell survival. Here, we review recent progress on the roles of Chemokines and Chemokine receptors in cancer-related inflammation, and discuss the mechanisms underlying Chemokine action in cancer that might facilitate the development of novel therapies in the future. © 2010 Elsevier Ltd.
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The good and the bad of Chemokines/Chemokine receptors in melanoma.
Pigment Cell & Melanoma Research, 2009Co-Authors: Ann Richmond, Jinming Yang, Yingjun SuAbstract:Chemokine ligand/receptor interactions affect melanoma cell growth, stimulate or inhibit angiogenesis, recruit leukocytes, promote metastasis, and alter the gene expression profile of the melanoma associated fibroblasts. Chemokine/Chemokine receptor interactions can protect against tumor development/growth or can stimulate melanoma tumor progression, tumor growth and metastasis. Metastatic melanoma cells express Chemokine receptors that play a major role in the specifying the organ site for metastasis, based upon receptor detection of the Chemokine gradient elaborated by a specific organ/tissue. A therapeutic approach that utilizes the protective benefit of Chemokines involves delivery of angiostatic Chemokines or Chemokines that stimulate the infiltration of cytotoxic T cells and natural killer T cells into the tumor microenvironment. An alternative approach that tackles the tumorigenic property of Chemokines uses Chemokine antibodies or Chemokine receptor antagonists to target the growth and metastatic properties of these interactions. Based upon our current understanding of the role of Chemokine-mediated inflammation in cancer, it is important that we learn to appropriately regulate the Chemokine contribution to the tumorigenic `cytokine/Chemokine storm', and to metastasis.
