The Experts below are selected from a list of 1116 Experts worldwide ranked by ideXlab platform

Joanna Mika - One of the best experts on this subject based on the ideXlab platform.

  • The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain
    Immunology, 2020
    Co-Authors: Katarzyna Pawlik, Anna Piotrowska, Klaudia Kwiatkowski, Katarzyna Ciapała, Katarzyna Popiolek-barczyk, Wioletta Makuch, Joanna Mika
    Abstract:

    A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant up-regulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA-1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as interleukin-1β (IL-1β), IL-6 and IL-18. The data obtained provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid-induced analgesia through the modulation of neuroimmune interactions.

  • Changes in macrophage inflammatory protein-1 (MIP-1) family members expression induced by traumatic brain injury in mice.
    Immunobiology, 2020
    Co-Authors: Agata Ciechanowska, Katarzyna Pawlik, Katarzyna Ciapała, Katarzyna Popiolek-barczyk, Marco Oggioni, Domenico Mercurio, Maria Grazia De Simoni, Joanna Mika
    Abstract:

    A deep knowledge of the profound immunological response induced by traumatic brain injury (TBI) raises the possibility of novel therapeutic interventions. Existing studies have highlighted the important roles of C-C motif ligands in the development of neuroinflammation after brain injury; however, the participation of macrophage inflammatory protein-1 (MIP-1) family members in this phenomenon is still undefined. Therefore, the goal of our study was to evaluate changes in macrophage inflammatory protein-1 (MIP-1) family members (CCL3, CCL4, and CCL9) and their receptors (CCR1 and CCR5) in a mouse model of TBI (induced by controlled cortical impact (CCI)). We also investigated the pattern of activation of immunological cells (such as neutrophils, microglia and astroglia), which on one hand express CCR1/CCR5, and on the other hand might be a source of the tested chemokines in the injured brain. We investigated changes in mRNA (RT-qPCR) and/or protein (ELISA and Western blot) expression in brain structures (the cortex, hippocampus, thalamus, and striatum) at different time points (24 h, 4 days, 7 days, 2 weeks, and/or 5 weeks) after trauma. Our time-course studies revealed the upregulation of the mRNA expression of all members of the MIP-1 family (CCL3, CCL4, and CCL9) in all tested brain structures, mainly in the early stages after injury. A similar pattern of activation was observed at the protein level in the cortex and thalamus, where the strongest activation was observed 1 day after CCI; however, we did not observe any change in CCL3 in the thalamus. Analyses of CCR1 and CCR5 demonstrated the upregulation of the mRNA expression of both receptors in all tested cerebral structures, mainly in the early phases post injury (24 h, 4 days and 7 days). Protein analysis showed the upregulation of CCR1 and CCR5 in the thalamus 24 h after TBI, but we did not detect any change in the cortex. We also observed the upregulation of neutrophil marker (MPO) at the early time points (24 h and 7 days) in the cortex, while the profound activation of microglia (IBA-1) and astroglia (GFAP) was observed mainly on day 7. Our findings highlight for the first time that CCL3, CCL4, CCL9 and their receptors offer promising targets for influencing secondary neuronal injury and improving TBI therapy. The results suggest that the MIP-1 family is an important target for pharmacological intervention for brain injury.

  • Involvement of Macrophage Inflammatory Protein-1 Family Members in the Development of Diabetic Neuropathy and Their Contribution to Effectiveness of Morphine
    Frontiers in immunology, 2018
    Co-Authors: Ewelina Rojewska, Anna Piotrowska, Magdalena Zychowska, Grzegorz Kreiner, Irena Nalepa, Joanna Mika
    Abstract:

    Current investigations underline the important roles of C-C motif ligands in the development of neuropathic pain; however, their participation in diabetic neuropathy is still undefined. Therefore, the goal of our study was to evaluate the participation of macrophage inflammatory protein-1 (MIP-1) family members (CCL3, CCL4, CCL9) in a streptozotocin (STZ) induced mouse model of diabetic neuropathic pain. Single intrathecal administration of each MIP-1 member (10, 100 or 500ng/5ul) in naive mice evoked hypersensitivity to mechanical (von Frey test) and thermal (cold plate test) stimuli. Concomitantly, protein analysis has shown that, 7 days following STZ injection, the levels of CCL3 and CCL9 (but not CCL4) are increased in the lumbar spinal cord. Performed additionally, immunofluorescence staining undoubtedly revealed that CCL3, CCL9 and their receptors (CCR1 and CCR5) are expressed predominantly by neurons. In vitro studies provided evidence that the observed expression of CCL3 and CCL9 may be partially of glial origin, however this observation was only partially possible to confirm by immunohistochemical study. Single intrathecal administration of CCL3 or CCL9 neutralizing antibody (2 and 4ug/5ul) delayed neuropathic pain symptoms as measured at day 7 following STZ administration. Single intrathecal injection of a CCR1 antagonist (J113863; 15 and 20ug/5ul) also attenuated pain-related behavior as evaluated at day 7 after STZ. Both neutralizing antibodies, as well as the CCR1 antagonist, enhanced the effectiveness of morphine in STZ-induced diabetic neuropathy. These findings highlight the important roles of CCL3 and CCL9 in the pathology of diabetic neuropathic pain and suggest that they play pivotal roles in opioid analgesia.

Fernando Q. Cunha - One of the best experts on this subject based on the ideXlab platform.

  • mip 1α ccl3 acting on the ccr1 receptor mediates neutrophil migration in immune inflammation via sequential release of tnf α and ltb4
    Journal of Leukocyte Biology, 2005
    Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. Cunha
    Abstract:

    In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced neutrophil migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent neutrophil migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce neutrophil migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.

  • mip 1α ccl3 acting on the ccr1 receptor mediates neutrophil migration in immune inflammation via sequential release of tnf α and ltb4
    Journal of Leukocyte Biology, 2005
    Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. Cunha
    Abstract:

    In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced neutrophil migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent neutrophil migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce neutrophil migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.

  • mip 1α ccl3 acting on the ccr1 receptor mediates neutrophil migration in immune inflammation via sequential release of tnf α and ltb4
    Journal of Leukocyte Biology, 2005
    Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, Joao Santana Da Silva, Fernando Q. Cunha
    Abstract:

    In the present study, we investigated the involvement of macrophage-inflammatory protein-1alpha (MIP-1alpha)[CC chemokine ligand 3 (CCL3)], MIP-1beta[CCL4], regulated on activation, normal T expressed and secreted (RANTES)[CCL5], and CC chemokine receptors (CCRs) on neutrophil migration in murine immune inflammation. Previously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor alpha (TNF-alpha) and leukotriene B(4)(LTB(4)). Herein, we show increased mRNA expression for MIP-1alpha[CCL3], MIP-1beta[CCL4], RANTES[CCL5], and CCR1 in peritoneal cells harvested from OVA-challenged, immunized mice, as well as MIP-1alpha[CCL3] and RANTES[CCL5] but not MIP-1beta[CCL4] proteins in the peritoneal exudates. OVA-induced neutrophil migration response was muted in immunized MIP-1alpha[CCL3](-/-) mice, but it was not inhibited by treatment with antibodies against RANTES[CCL5] or MIP-1beta[CCL4]. MIP-1alpha[CCL3] mediated neutrophil migration in immunized mice through induction of TNF-alpha and LTB(4) synthesis, as these mediators were detected in the exudates harvested from OVA-challenged immunized wild-type but not MIP-1alpha[CCL3](-/-) mice; administration of MIP-1alpha[CCL3] induced a dose-dependent neutrophil migration, which was inhibited by treatment with an anti-TNF-alpha antibody in TNF receptor 1 (p55(-/-))-deficient mice or by MK 886 (a 5-lipoxygenase inhibitor); and MIP-1alpha[CCL3] failed to induce LTB(4) production in p55(-/-) mice. MIP-1alpha[CCL3] used CCR1 to promote neutrophil recruitment, as OVA or MIP-1alpha[CCL3] failed to induce neutrophil migration in CCR1(-/-) mice, in contrast to CCR5(-/-) mice. In summary, we have demonstrated that neutrophil migration observed in this model of immune inflammation is mediated by MIP-1alpha[CCL3], which via CCR1, induces the sequential release of TNF-alpha and LTB(4). Therefore, whether a similar pathway mediates neutrophil migration in human immune-inflammatory diseases, the development of specific CCR1 antagonists might have a therapeutic potential.

Claudio Canetti - One of the best experts on this subject based on the ideXlab platform.

  • mip 1α ccl3 acting on the ccr1 receptor mediates neutrophil migration in immune inflammation via sequential release of tnf α and ltb4
    Journal of Leukocyte Biology, 2005
    Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. Cunha
    Abstract:

    In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced neutrophil migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent neutrophil migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce neutrophil migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.

  • mip 1α ccl3 acting on the ccr1 receptor mediates neutrophil migration in immune inflammation via sequential release of tnf α and ltb4
    Journal of Leukocyte Biology, 2005
    Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. Cunha
    Abstract:

    In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced neutrophil migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent neutrophil migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce neutrophil migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.

  • mip 1α ccl3 acting on the ccr1 receptor mediates neutrophil migration in immune inflammation via sequential release of tnf α and ltb4
    Journal of Leukocyte Biology, 2005
    Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, Joao Santana Da Silva, Fernando Q. Cunha
    Abstract:

    In the present study, we investigated the involvement of macrophage-inflammatory protein-1alpha (MIP-1alpha)[CC chemokine ligand 3 (CCL3)], MIP-1beta[CCL4], regulated on activation, normal T expressed and secreted (RANTES)[CCL5], and CC chemokine receptors (CCRs) on neutrophil migration in murine immune inflammation. Previously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor alpha (TNF-alpha) and leukotriene B(4)(LTB(4)). Herein, we show increased mRNA expression for MIP-1alpha[CCL3], MIP-1beta[CCL4], RANTES[CCL5], and CCR1 in peritoneal cells harvested from OVA-challenged, immunized mice, as well as MIP-1alpha[CCL3] and RANTES[CCL5] but not MIP-1beta[CCL4] proteins in the peritoneal exudates. OVA-induced neutrophil migration response was muted in immunized MIP-1alpha[CCL3](-/-) mice, but it was not inhibited by treatment with antibodies against RANTES[CCL5] or MIP-1beta[CCL4]. MIP-1alpha[CCL3] mediated neutrophil migration in immunized mice through induction of TNF-alpha and LTB(4) synthesis, as these mediators were detected in the exudates harvested from OVA-challenged immunized wild-type but not MIP-1alpha[CCL3](-/-) mice; administration of MIP-1alpha[CCL3] induced a dose-dependent neutrophil migration, which was inhibited by treatment with an anti-TNF-alpha antibody in TNF receptor 1 (p55(-/-))-deficient mice or by MK 886 (a 5-lipoxygenase inhibitor); and MIP-1alpha[CCL3] failed to induce LTB(4) production in p55(-/-) mice. MIP-1alpha[CCL3] used CCR1 to promote neutrophil recruitment, as OVA or MIP-1alpha[CCL3] failed to induce neutrophil migration in CCR1(-/-) mice, in contrast to CCR5(-/-) mice. In summary, we have demonstrated that neutrophil migration observed in this model of immune inflammation is mediated by MIP-1alpha[CCL3], which via CCR1, induces the sequential release of TNF-alpha and LTB(4). Therefore, whether a similar pathway mediates neutrophil migration in human immune-inflammatory diseases, the development of specific CCR1 antagonists might have a therapeutic potential.

Janeusa T Souto - One of the best experts on this subject based on the ideXlab platform.

  • mip 1α ccl3 acting on the ccr1 receptor mediates neutrophil migration in immune inflammation via sequential release of tnf α and ltb4
    Journal of Leukocyte Biology, 2005
    Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. Cunha
    Abstract:

    In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced neutrophil migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent neutrophil migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce neutrophil migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.

  • mip 1α ccl3 acting on the ccr1 receptor mediates neutrophil migration in immune inflammation via sequential release of tnf α and ltb4
    Journal of Leukocyte Biology, 2005
    Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, João S. Silva, Fernando Q. Cunha
    Abstract:

    In the present study, we investigated the involvement of macrophage-inflammatory pro- tein-1 (MIP-1)(CC chemokine ligand 3 (CCL3)), MIP-1(CCL4), regulated on activation, normal T expressed and secreted (RANTES)(CCL5), and CC chemokine receptors (CCRs) on neutrophil mi- gration in murine immune inflammation. Previ- ously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor (TNF-) and leukotriene B 4 (LTB 4 ). Herein, we show increased mRNA expression for MIP- 1(CCL3), MIP-1(CCL4), RANTES(CCL5), and CCR1 in peritoneal cells harvested from OVA-chal- lenged, immunized mice, as well as MIP-1(CCL3) and RANTES(CCL5) but not MIP-1(CCL4) proteins in the peritoneal exudates. OVA-induced neutrophil migration response was muted in immunized MIP- 1(CCL3) / mice, but it was not inhibited by treat- ment with antibodies against RANTES(CCL5) or MIP-1(CCL4). MIP-1(CCL3) mediated neutro- phil migration in immunized mice through induc- tion of TNF- and LTB4 synthesis, as these medi- ators were detected in the exudates harvested from OVA-challenged, immunized wild-type but not MIP-1(CCL3) / mice; administration of MIP- 1(CCL3) induced a dose-dependent neutrophil migration, which was inhibited by treatment with an anti-TNF- antibody in TNF receptor 1 (p55 / )- deficient mice or by MK 886 (a 5-lipoxygenase in- hibitor); and MIP-1(CCL3) failed to induce LTB 4 production in p55 / mice. MIP-1(CCL3) used CCR1 to promote neutrophil recruitment, as OVA or MIP-1(CCL3) failed to induce neutrophil migration in CCR1 / mice, in contrast to CCR5 / mice. In summary, we have demonstrated that neutrophil mi- gration observed in this model of immune inflamma- tion is mediated by MIP-1(CCL3), which via CCR1, induces the sequential release of TNF- and LTB4. Therefore, whether a similar pathway mediates neu- trophil migration in human immune-inflammatory diseases, the development of specific CCR1 antago- nists might have a therapeutic potential. J. Leukoc. Biol. 78: 000-000; 2005.

  • mip 1α ccl3 acting on the ccr1 receptor mediates neutrophil migration in immune inflammation via sequential release of tnf α and ltb4
    Journal of Leukocyte Biology, 2005
    Co-Authors: Cleber D L Ramos, Janeusa T Souto, Cory M Hogaboam, Claudio Canetti, Sergio H Ferreira, Joao Santana Da Silva, Fernando Q. Cunha
    Abstract:

    In the present study, we investigated the involvement of macrophage-inflammatory protein-1alpha (MIP-1alpha)[CC chemokine ligand 3 (CCL3)], MIP-1beta[CCL4], regulated on activation, normal T expressed and secreted (RANTES)[CCL5], and CC chemokine receptors (CCRs) on neutrophil migration in murine immune inflammation. Previously, we showed that ovalbumin (OVA)-triggered neutrophil migration in immunized mice depends on the sequential release of tumor necrosis factor alpha (TNF-alpha) and leukotriene B(4)(LTB(4)). Herein, we show increased mRNA expression for MIP-1alpha[CCL3], MIP-1beta[CCL4], RANTES[CCL5], and CCR1 in peritoneal cells harvested from OVA-challenged, immunized mice, as well as MIP-1alpha[CCL3] and RANTES[CCL5] but not MIP-1beta[CCL4] proteins in the peritoneal exudates. OVA-induced neutrophil migration response was muted in immunized MIP-1alpha[CCL3](-/-) mice, but it was not inhibited by treatment with antibodies against RANTES[CCL5] or MIP-1beta[CCL4]. MIP-1alpha[CCL3] mediated neutrophil migration in immunized mice through induction of TNF-alpha and LTB(4) synthesis, as these mediators were detected in the exudates harvested from OVA-challenged immunized wild-type but not MIP-1alpha[CCL3](-/-) mice; administration of MIP-1alpha[CCL3] induced a dose-dependent neutrophil migration, which was inhibited by treatment with an anti-TNF-alpha antibody in TNF receptor 1 (p55(-/-))-deficient mice or by MK 886 (a 5-lipoxygenase inhibitor); and MIP-1alpha[CCL3] failed to induce LTB(4) production in p55(-/-) mice. MIP-1alpha[CCL3] used CCR1 to promote neutrophil recruitment, as OVA or MIP-1alpha[CCL3] failed to induce neutrophil migration in CCR1(-/-) mice, in contrast to CCR5(-/-) mice. In summary, we have demonstrated that neutrophil migration observed in this model of immune inflammation is mediated by MIP-1alpha[CCL3], which via CCR1, induces the sequential release of TNF-alpha and LTB(4). Therefore, whether a similar pathway mediates neutrophil migration in human immune-inflammatory diseases, the development of specific CCR1 antagonists might have a therapeutic potential.

Thomas J Schall - One of the best experts on this subject based on the ideXlab platform.

  • proteolytic activation of alternative ccr1 ligands in inflammation
    Journal of Immunology, 2005
    Co-Authors: Robert D Berahovich, Zhenhua Miao, Yu Wang, Brett Premack, Maureen Howard, Thomas J Schall
    Abstract:

    Although chemokines CCL3/MIP-1α and CCL5/RANTES are considered to be primary CCR1 ligands in inflammatory responses, alternative CCR1 ligands have also been described. Indeed, four such chemokines, CCL6/C10/MIP-related protein-1, CCL9/MIP-1γ/MIP-related protein-2, CCL15/MIP-1δ/hemofiltrate CC chemokine-2/leukotactin-1, and CCL23/CKβ8/myeloid progenitor inhibitory factor-1, are unique in possessing a separately encoded N-terminal domain of 16–20 residues and two additional precisely positioned cysteines that form a third disulfide bridge. In vitro, these four chemokines are weak CCR1 agonists, but potency can be increased up to 1000-fold by engineered or expression-associated N-terminal truncations. We examined the ability of proinflammatory proteases, human cell supernatants, or physiological fluids to perform N-terminal truncations of these chemokines and thereby activate their functions. Remarkably, most of the proteases and fluids removed the N-terminal domains from all four chemokines, but were relatively unable to cleave the truncated forms further. The truncated chemokines exhibited up to 1000-fold increases in CCR1-mediated signaling and chemotaxis assays in vitro. In addition, N-terminally truncated CCL15/MIP-1δ and CCL23/CKβ8, but not CCL3/MIP-1α or CCL5/RANTES, were detected at relatively high levels in synovial fluids from rheumatoid arthritis patients. These data suggest that alternative CCR1 ligands are converted into potent chemoattractants by proteases released during inflammatory responses in vivo.

  • proteolytic activation of alternative ccr1 ligands in inflammation
    Journal of Immunology, 2005
    Co-Authors: Robert D Berahovich, Zhenhua Miao, Yu Wang, Brett Premack, Maureen Howard, Thomas J Schall
    Abstract:

    Although chemokines CCL3/MIP-1alpha and CCL5/RANTES are considered to be primary CCR1 ligands in inflammatory responses, alternative CCR1 ligands have also been described. Indeed, four such chemokines, CCL6/C10/MIP-related protein-1, CCL9/MIP-1gamma/MIP-related protein-2, CCL15/MIP-1delta/hemofiltrate CC chemokine-2/leukotactin-1, and CCL23/CKbeta8/myeloid progenitor inhibitory factor-1, are unique in possessing a separately encoded N-terminal domain of 16-20 residues and two additional precisely positioned cysteines that form a third disulfide bridge. In vitro, these four chemokines are weak CCR1 agonists, but potency can be increased up to 1000-fold by engineered or expression-associated N-terminal truncations. We examined the ability of proinflammatory proteases, human cell supernatants, or physiological fluids to perform N-terminal truncations of these chemokines and thereby activate their functions. Remarkably, most of the proteases and fluids removed the N-terminal domains from all four chemokines, but were relatively unable to cleave the truncated forms further. The truncated chemokines exhibited up to 1000-fold increases in CCR1-mediated signaling and chemotaxis assays in vitro. In addition, N-terminally truncated CCL15/MIP-1delta and CCL23/CKbeta8, but not CCL3/MIP-1alpha or CCL5/RANTES, were detected at relatively high levels in synovial fluids from rheumatoid arthritis patients. These data suggest that alternative CCR1 ligands are converted into potent chemoattractants by proteases released during inflammatory responses in vivo.