The Experts below are selected from a list of 837570 Experts worldwide ranked by ideXlab platform
João S. Silva - One of the best experts on this subject based on the ideXlab platform.
-
evidences of the cooperative role of the chemokines ccl3 CCL4 and ccl5 and its receptors ccr1 and ccr5 in rankl cell migration throughout experimental periodontitis in mice
Bone, 2010Co-Authors: Carlos Eduardo Repeke, Samuel B Ferreira, Elcia Maria Varize Silveira, Mario Julio Avilacampos, Marcela Claudino, João S. Silva, Gerson Francisco De Assis, Gustavo Pompermaier GarletAbstract:Periodontal disease (PD) is characterized by the inflammatory bone resorption in response to the bacterial challenge, in a host response that involves a series of chemokines supposed to control cell influx into periodontal tissues and determine disease outcome. In this study, we investigated the role of chemokines and its receptors in the immunoregulation of experimental PD in mice. Aggregatibacter actinomycetemcomitans-infected C57Bl/6 (WT) mice developed an intense inflammatory reaction and severe alveolar bone resorption, associated with a high expression of CCL3 and the migration of CCR5+, CCR1+ and RANKL+ cells to periodontal tissues. However, CCL3KO-infected mice developed a similar disease phenotype than WT strain, characterized by the similar expression of cytokines (TNF-α, IFN-γ and IL-10), osteoclastogenic factors (RANKL and OPG) and MMPs (MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-3), and similar patterns of CCR1+, CCR5+ and RANKL+ cell migration. The apparent lack of function for CCL3 is possible due the relative redundancy of chemokine system, since chemokines such as CCL4 and CCL5, which share the receptors CCR1 and CCR5 with CCL3, present a similar kinetics of expression than CCL3. Accordingly, CCL4 and CCL5 kinetics of expression after experimental periodontal infection remain unaltered regardless the presence/absence of CCL3. Conversely, the individual absence of CCR1 and CCR5 resulted in a decrease of leukocyte infiltration and alveolar bone loss. When CCR1 and CCR5 were simultaneously inhibited by met-RANTES treatment a significantly more effective attenuation of periodontitis progression was verified, associated with lower values of bone loss and decreased counts of leukocytes in periodontal tissues. Our results suggest that the absence of CCL3 does not affect the development of experimental PD in mice, probably due to the presence of homologous chemokines CCL4 and CCL5 that overcome the absence of this chemokine. In addition, our data demonstrate that the absence of chemokine receptors CCR1+ and CCR5+ attenuate of inflammatory bone resorption. Finally, our data shows data the simultaneous blockade of CCR1 and CCR5 with MetRANTEs presents a more pronounced effect in the arrest of disease progression, demonstrating the cooperative role of such receptors in the inflammatory bone resorption process throughout experimental PD.
-
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, 2005Co-Authors: Cleber D L Ramos, Cory M Hogaboam, João S. Silva, Claudio Canetti, Janeusa T Souto, Sergio H Ferreira, Fernando Q CunhaAbstract: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.
-
actinobacillus actinomycetemcomitans induced periodontal disease in mice patterns of cytokine chemokine and chemokine receptor expression and leukocyte migration
Microbes and Infection, 2005Co-Authors: Gustavo Pompermaier Garlet, Mario Julio Avilacampos, Cristiane M Milanezi, Beatriz Rossetti Ferreira, João S. SilvaAbstract:Although the pathogenesis of periodontal disease (PD) is not well known, cytokines, chemotactic factors and inflammatory cells are certainly involved in the disease outcome. Here, we characterized the evolution of the PD induced by Actinobacillus actinomycetemcomitans in mice, showing that oral inoculation of these bacteria leads to the migration of leukocytes to periodontal tissues and marked alveolar bone resorption. We found the expression of pro-inflammatory and Th1-type cytokines including TNF-a, IFN-c and IL-12 in periodontal tissues after infection with A. actinomycetemcomitans, from the early stages after infection and throughout the course of the disease. Similar kinetics of expression were found for the chemokines CCL5, CCL4, CCL3 and CXCL10 and for the receptors CCR5 and CXCR3, all of them linked to the Th1-type pattern. The expression of the Th2-type mediators IL-10, CCL1 and their receptors CCR4 and CCR8 was detected only after 30 days of infection, determining a time-dependent mixed pattern of polarized immune response. The chemokine expression was correlated with the presence of polymorphonuclear leukocytes, macrophages, CD4 and CD8 lymphocytes, and B cells in the inflammatory infiltrate. Interestingly, during the predominance of the Th1-type response, a sharp increase in the number of inflammatory cells and intense bone loss was seen. By contrast, after the increased expression of Th2-type mediators, the number of inflammatory cells remained constant. Our data demonstrate that mice subjected to oral inoculation of A. actinomycetemcomitans represent a useful model for the study of PD. In addition, our results suggest that expression of cytokines and chemokines can drive the selective recruitment of leukocyte subsets to periodontal tissues, which could determine the stable or progressive nature of the lesion. © 2005 Elsevier SAS. All rights reserved.
Marina O Gomzikova - One of the best experts on this subject based on the ideXlab platform.
-
immunosuppressive properties of cytochalasin b induced membrane vesicles of mesenchymal stem cells comparing with extracellular vesicles derived from mesenchymal stem cells
Scientific Reports, 2020Co-Authors: Marina O Gomzikova, A M Aimaletdinov, Oksana V Bondar, I G Starostina, N V Gorshkova, Olga Neustroeva, Sevindzh Kletukhina, Sirina V Kurbangaleeva, Vyacheslav V VorobevAbstract:Extracellular vesicles derived from mesenchymal stem cells (MSCs) represent a novel approach for regenerative and immunosuppressive therapy. Recently, cytochalasin B-induced microvesicles (CIMVs) were shown to be effective drug delivery mediators. However, little is known about their immunological properties. We propose that the immunophenotype and molecular composition of these vesicles could contribute to the therapeutic efficacy of CIMVs. To address this issue, CIMVs were generated from murine MSC (CIMVs-MSCs) and their cytokine content and surface marker expression determined. For the first time, we show that CIMVs-MSCs retain parental MSCs phenotype (Sca-1+, CD49e+, CD44+, CD45−). Also, CIMVs-MSCs contained a cytokine repertoire reflective of the parental MSCs, including IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12(p40), IL-13, IL-17, CCL2, CCL3, CCL4, CCL5, CCL11, G-CSF, GM-CSF and TNF-α. Next, we evaluated the immune-modulating properties of CIMVs-MSCs in vivo using standard preclinical tests. MSCs and CIMVs-MSCs reduced serum levels of anti-sheep red blood cell antibody and have limited effects on neutrophil and peritoneal macrophage activity. We compared the immunomodulatory effect of MSCs, CIMVs and EVs. We observed no immunosuppression in mice pretreated with natural EVs, whereas MSCs and CIMVs-MSCs suppressed antibody production in vivo. Additionally, we have investigated the biodistribution of CIMVs-MSCs in vivo and demonstrated that CIMVs-MSCs localized in liver, lung, brain, heart, spleen and kidneys 48 h after intravenous injection and can be detected 14 days after subcutaneous and intramuscular injection. Collectively our data demonstrates immunomodulatory efficacy of CIMVs and supports their further preclinical testing as an effective therapeutic delivery modality.
Koichi Takahashi - One of the best experts on this subject based on the ideXlab platform.
-
ccl3 and CCL4 are biomarkers for b cell receptor pathway activation and prognostic serum markers in diffuse large b cell lymphoma
British Journal of Haematology, 2015Co-Authors: Koichi Takahashi, Mariela Sivina, Julia Hoellenriegel, Yasuhiro Oki, Fredrick B Hagemeister, Luis Fayad, Jorge E Romaguera, Nathan Fowler, Michelle A FanaleAbstract:B cell receptor (BCR) signalling is an important pathway in diffuse large B cell lymphoma (DLBCL). In response to BCR triggering, normal and malignant B cells secrete the chemokines CCL3 and CCL4 to attract accessory cells to the tissue microenvironment. We measured CCL3 and CCL4 serum concentrations in 102 patients with newly diagnosed DLBCL by enzyme-linked immunosorbent assay, investigated their prognostic impact and validated our findings in an independent cohort of 51 patient samples. We also tested CCL3 and CCL4 secretion by DLBCL cells, and the influence of BTK inhibitors on the secretion of these chemokines. High CCL3 (≥40 pg/ml) serum concentrations correlated with higher international prognostic index, lactate dehydrogenase and β2 microglobulin, as did CCL4 (≥180 pg/ml) with advanced Ann Arbor stages. High CCL3 levels correlated with significantly shorter progression-free and overall survival. The in vitro studies demonstrated that activated B cell-like, but not germinal centre B cell-like DLBCL cells, secrete high levels of CCL3 and CCL4 after BCR triggering, which was exquisitely sensitive to BCR pathway inhibition. These findings support CCL3 and CCL4 protein concentrations as biomarkers for BCR pathway activation and prognosis in DLBCL.
Xuetao Cao - One of the best experts on this subject based on the ideXlab platform.
-
chemokine containing exosomes are released from heat stressed tumor cells via lipid raft dependent pathway and act as efficient tumor vaccine
Journal of Immunology, 2011Co-Authors: Taoyong Chen, Jun Guo, Mingjin Yang, Xuhui Zhu, Xuetao CaoAbstract:Exosomes derived from dendritic cells or tumor cells are a population of nanometer-sized membrane vesicles that can induce specific antitumor immunity. During investigation of the effects of hyperthermia on antitumor immune response, we found that exosomes derived from heat-stressed tumor cells (HS-TEX) could chemoattract and activate dendritic cells (DC) and T cells more potently than that by conventional tumor-derived exosomes. We show that HS-TEX contain chemokines, such as CCL2, CCL3, CCL4, CCL5, and CCL20, and the chemokine-containing HS-TEX are functionally competent in chemoattracting CD11c(+) DC and CD4(+)/CD8(+) T cells both in vitro and in vivo. Moreover, the production of chemokine-containing HS-TEX could be inhibited by ATP inhibitor, calcium chelator, and cholesterol scavenger, indicating that the mobilization of chemokines into exosomes was ATP- and calcium-dependent and via a lipid raft-dependent pathway. We consistently found that the intracellular chemokines could be enriched in lipid rafts after heat stress. Accordingly, intratumoral injection of HS-TEX could induce specific antitumor immune response more efficiently than that by tumor-derived exosomes, thus inhibiting tumor growth and prolonging survival of tumor-bearing mice more significantly. Therefore, our results demonstrate that exosomes derived from HS-TEX represent a kind of efficient tumor vaccine and can chemoattract and activate DC and T cells, inducing more potent antitumor immune response. Release of chemokines through exosomes via lipid raft-dependent pathway may be a new method of chemokine exocytosis.
Gustavo Pompermaier Garlet - One of the best experts on this subject based on the ideXlab platform.
-
evidences of the cooperative role of the chemokines ccl3 CCL4 and ccl5 and its receptors ccr1 and ccr5 in rankl cell migration throughout experimental periodontitis in mice
Bone, 2010Co-Authors: Carlos Eduardo Repeke, Samuel B Ferreira, Elcia Maria Varize Silveira, Mario Julio Avilacampos, Marcela Claudino, João S. Silva, Gerson Francisco De Assis, Gustavo Pompermaier GarletAbstract:Periodontal disease (PD) is characterized by the inflammatory bone resorption in response to the bacterial challenge, in a host response that involves a series of chemokines supposed to control cell influx into periodontal tissues and determine disease outcome. In this study, we investigated the role of chemokines and its receptors in the immunoregulation of experimental PD in mice. Aggregatibacter actinomycetemcomitans-infected C57Bl/6 (WT) mice developed an intense inflammatory reaction and severe alveolar bone resorption, associated with a high expression of CCL3 and the migration of CCR5+, CCR1+ and RANKL+ cells to periodontal tissues. However, CCL3KO-infected mice developed a similar disease phenotype than WT strain, characterized by the similar expression of cytokines (TNF-α, IFN-γ and IL-10), osteoclastogenic factors (RANKL and OPG) and MMPs (MMP-1, MMP-2, MMP-3, TIMP-1 and TIMP-3), and similar patterns of CCR1+, CCR5+ and RANKL+ cell migration. The apparent lack of function for CCL3 is possible due the relative redundancy of chemokine system, since chemokines such as CCL4 and CCL5, which share the receptors CCR1 and CCR5 with CCL3, present a similar kinetics of expression than CCL3. Accordingly, CCL4 and CCL5 kinetics of expression after experimental periodontal infection remain unaltered regardless the presence/absence of CCL3. Conversely, the individual absence of CCR1 and CCR5 resulted in a decrease of leukocyte infiltration and alveolar bone loss. When CCR1 and CCR5 were simultaneously inhibited by met-RANTES treatment a significantly more effective attenuation of periodontitis progression was verified, associated with lower values of bone loss and decreased counts of leukocytes in periodontal tissues. Our results suggest that the absence of CCL3 does not affect the development of experimental PD in mice, probably due to the presence of homologous chemokines CCL4 and CCL5 that overcome the absence of this chemokine. In addition, our data demonstrate that the absence of chemokine receptors CCR1+ and CCR5+ attenuate of inflammatory bone resorption. Finally, our data shows data the simultaneous blockade of CCR1 and CCR5 with MetRANTEs presents a more pronounced effect in the arrest of disease progression, demonstrating the cooperative role of such receptors in the inflammatory bone resorption process throughout experimental PD.
-
actinobacillus actinomycetemcomitans induced periodontal disease in mice patterns of cytokine chemokine and chemokine receptor expression and leukocyte migration
Microbes and Infection, 2005Co-Authors: Gustavo Pompermaier Garlet, Mario Julio Avilacampos, Cristiane M Milanezi, Beatriz Rossetti Ferreira, João S. SilvaAbstract:Although the pathogenesis of periodontal disease (PD) is not well known, cytokines, chemotactic factors and inflammatory cells are certainly involved in the disease outcome. Here, we characterized the evolution of the PD induced by Actinobacillus actinomycetemcomitans in mice, showing that oral inoculation of these bacteria leads to the migration of leukocytes to periodontal tissues and marked alveolar bone resorption. We found the expression of pro-inflammatory and Th1-type cytokines including TNF-a, IFN-c and IL-12 in periodontal tissues after infection with A. actinomycetemcomitans, from the early stages after infection and throughout the course of the disease. Similar kinetics of expression were found for the chemokines CCL5, CCL4, CCL3 and CXCL10 and for the receptors CCR5 and CXCR3, all of them linked to the Th1-type pattern. The expression of the Th2-type mediators IL-10, CCL1 and their receptors CCR4 and CCR8 was detected only after 30 days of infection, determining a time-dependent mixed pattern of polarized immune response. The chemokine expression was correlated with the presence of polymorphonuclear leukocytes, macrophages, CD4 and CD8 lymphocytes, and B cells in the inflammatory infiltrate. Interestingly, during the predominance of the Th1-type response, a sharp increase in the number of inflammatory cells and intense bone loss was seen. By contrast, after the increased expression of Th2-type mediators, the number of inflammatory cells remained constant. Our data demonstrate that mice subjected to oral inoculation of A. actinomycetemcomitans represent a useful model for the study of PD. In addition, our results suggest that expression of cytokines and chemokines can drive the selective recruitment of leukocyte subsets to periodontal tissues, which could determine the stable or progressive nature of the lesion. © 2005 Elsevier SAS. All rights reserved.