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  1. AU="Neote, Kuldeep S"
  2. AU="Shen, Congcong"
  3. AU="Rahi, Kosar"
  4. AU="Channabasavaiah, Jagadish Puralae"
  5. AU="Anselmi, Maurizio"
  6. AU="Chauhan, D."
  7. AU="Nicoll, Roger A"
  8. AU="Kwon, Young-Sam"
  9. AU="Mihwa Lee"
  10. AU="Yuanting Jin"
  11. AU="Ter Haar, Eva"
  12. AU="Wolin, Dan L"
  13. AU="Zhang, Tenan"
  14. AU="Piedrafita, Lídia"
  15. AU="Nandy, Ananya"
  16. AU="Bansemer, Sven"
  17. AU="Kochetov, O"
  18. AU="Liu, Fen"

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  1. Artikel: The human specific CCR1 antagonist CP-481,715 inhibits cell infiltration and inflammatory responses in human CCR1 transgenic mice.

    Gladue, Ronald P / Cole, Susan H / Roach, Marsha L / Tylaska, Laurie A / Nelson, Robin T / Shepard, Richard M / McNeish, John D / Ogborne, Kevin T / Neote, Kuldeep S

    Journal of immunology (Baltimore, Md. : 1950)

    2006  Band 176, Heft 5, Seite(n) 3141–3148

    Abstract: We previously described the in vitro characteristics of the potent and selective CCR1 antagonist, CP-481,715. In addition to being selective for CCR1 vs other chemokine receptors, CP-481,715 is also specific for human CCR1 (hCCR1), preventing its ... ...

    Abstract We previously described the in vitro characteristics of the potent and selective CCR1 antagonist, CP-481,715. In addition to being selective for CCR1 vs other chemokine receptors, CP-481,715 is also specific for human CCR1 (hCCR1), preventing its evaluation in classical animal models. To address this, we generated mice whereby murine CCR1 was replaced by hCCR1 (knockin) and used these animals to assess the anti-inflammatory properties of CP-481,715. Cells isolated from hCCR1 knockin mice were shown to express hCCR1 and migrate in response to both murine CCR1 and hCCR1 ligands. Furthermore, this migration is inhibited by CP-481,715 at dose levels comparable to those obtained with human cells. In animal models of cell infiltration, CP-481,715 inhibited CCL3-induced neutrophil infiltration into skin or into an air pouch with an ED50 of 0.2 mg/kg. CP-481,715 did not inhibit cell infiltration in wild-type animals expressing murine CCR1. In a more generalized model of inflammation, delayed-type hypersensitivity, CP-481,715 significantly inhibited footpad swelling and decreased the amount of IFN-gamma and IL-2 produced by isolated spleen cells from sensitized animals. It did not, however, induce tolerance to a subsequent challenge. These studies illustrate the utility of hCCR1 knockin animals to assess the activity of human specific CCR1 antagonists; demonstrate the ability of the CCR1 antagonist CP-481,715 to inhibit cell infiltration, inflammation, and Th1 cytokine responses in these animals; and suggest that CP-481,715 may be useful to modulate inflammatory responses in human disease.
    Mesh-Begriff(e) Actins/metabolism ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Cell Migration Inhibition ; Cells, Cultured ; Chemokine CCL3 ; Chemokine CCL4 ; Chemokines, CC/physiology ; Chemotaxis, Leukocyte/drug effects ; Chemotaxis, Leukocyte/immunology ; Cytokines/metabolism ; Humans ; Hypersensitivity, Delayed/drug therapy ; Hypersensitivity, Delayed/genetics ; Hypersensitivity, Delayed/pathology ; Macrophage Inflammatory Proteins/physiology ; Mice ; Mice, Inbred DBA ; Mice, Transgenic ; Quinoxalines/pharmacology ; Receptors, CCR1 ; Receptors, Chemokine/antagonists & inhibitors ; Receptors, Chemokine/genetics ; Stem Cells/immunology ; Stem Cells/pathology ; Th1 Cells/drug effects ; Th1 Cells/metabolism
    Chemische Substanzen Actins ; Anti-Inflammatory Agents, Non-Steroidal ; CCR1 protein, human ; Ccl3 protein, mouse ; Ccr1 protein, mouse ; Chemokine CCL3 ; Chemokine CCL4 ; Chemokines, CC ; Cytokines ; Macrophage Inflammatory Proteins ; Quinoxalines ; Receptors, CCR1 ; Receptors, Chemokine ; quinoxaline-2-carboxylic acid (4-carbamoyl-1-(3-fluorobenzyl)-2,7-dihydroxy-7-methyloctyl)amide
    Sprache Englisch
    Erscheinungsdatum 2006-01-11
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.176.5.3141
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Expression of rat I-TAC/CXCL11/SCYA11 during central nervous system inflammation: comparison with other CXCR3 ligands.

    McColl, Shaun R / Mahalingam, Surendran / Staykova, Maria / Tylaska, Laurie A / Fisher, Katherine E / Strick, Christine A / Gladue, Ronald P / Neote, Kuldeep S / Willenborg, David O

    Laboratory investigation; a journal of technical methods and pathology

    2003  Band 84, Heft 11, Seite(n) 1418–1429

    Abstract: The chemokines are a large gene superfamily with critical roles in development and immunity. The chemokine receptor CXCR3 appears to play a major role in the trafficking of activated Th1 lymphocytes. There are at least three major ligands for CXCR3: mig/ ... ...

    Abstract The chemokines are a large gene superfamily with critical roles in development and immunity. The chemokine receptor CXCR3 appears to play a major role in the trafficking of activated Th1 lymphocytes. There are at least three major ligands for CXCR3: mig/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, and of these three ligands, CXCL11 is the least well-characterized. In this study, we have cloned a rat ortholog of CXCL11, evaluated its function, and examined its expression in the Th-1-mediated disease, experimental autoimmune encephalomyelitis (EAE) in the rat. Based on its predicted primary amino-acid sequence, rat I-TAC/CXCL11 was synthesized and shown to induce chemotaxis of activated rat T lymphocytes in vitro and the in vivo migration of T lymphocytes when injected into the skin. I-TAC/CXCL11 expression, as determined by RT-PCR, increased in lymph node and spinal cord tissue collected from rats in which EAE had been actively induced, and in spinal cord tissue from rats in which EAE had been passively induced. The kinetics of expression were similar to that of CXCR3 and IP-10/CXCL10, although expression of both CXCR3 and IP-10/CXCL10 was more intense than that of I-TAC/CXCL11 and increased more rapidly in both lymph nodes and the spinal cord. Only minor levels of expression of the related chemokine mig/CXCL9 were observed. Immunohistochemistry revealed that the major cellular source of I-TAC/CXCL11 in the central nervous system (CNS) during EAE is likely to be the astrocyte. Together, these data indicate that I-TAC/CXCL11 is expressed in the CNS during the clinical phase of EAE. However, the observation that I-TAC/CXCL11 is expressed after receptor expression is detected suggests that it is not essential for the initial migration of CXCR3-bearing cells into the CNS.
    Mesh-Begriff(e) Amino Acid Sequence ; Animals ; Cells, Cultured ; Chemokine CCL11 ; Chemokine CXCL11 ; Chemokines, CC/genetics ; Chemokines, CC/metabolism ; Chemokines, CXC/genetics ; Chemokines, CXC/metabolism ; Chemokines, CXC/pharmacology ; Chemotaxis/drug effects ; Cloning, Molecular ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; Encephalomyelitis, Autoimmune, Experimental/pathology ; Female ; Humans ; Ligands ; Lymph Nodes/drug effects ; Lymph Nodes/pathology ; Molecular Sequence Data ; RNA, Messenger/metabolism ; Rats ; Rats, Inbred Lew ; Receptors, CXCR3 ; Receptors, Chemokine/genetics ; Receptors, Chemokine/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Spleen/drug effects ; Spleen/pathology ; T-Lymphocytes/drug effects ; T-Lymphocytes/pathology
    Chemische Substanzen CCL11 protein, human ; CXCL11 protein, human ; CXCR3 protein, human ; Ccl11 protein, rat ; Chemokine CCL11 ; Chemokine CXCL11 ; Chemokines, CC ; Chemokines, CXC ; Cxcl11 protein, rat ; Cxcr3 protein, rat ; Ligands ; RNA, Messenger ; Receptors, CXCR3 ; Receptors, Chemokine
    Sprache Englisch
    Erscheinungsdatum 2003-05-14
    Erscheinungsland United States
    Dokumenttyp Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80178-1
    ISSN 1530-0307 ; 0023-6837
    ISSN (online) 1530-0307
    ISSN 0023-6837
    DOI 10.1038/labinvest.3700155
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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