The Experts below are selected from a list of 5376 Experts worldwide ranked by ideXlab platform
Evi Kostenis - One of the best experts on this subject based on the ideXlab platform.
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antagonism of the prostaglandin d2 receptor crth2 attenuates Asthma Pathology in mouse eosinophilic airway inflammation
Respiratory Research, 2007Co-Authors: Lena Uller, Lisa Alenmyr, Magnus Korsgren, Trond Ulven, Thomas Hogberg, Gunnar Andersson, Carl G A Persson, Jesper Mosolff Mathiesen, Evi KostenisAbstract:Background Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic Asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit Asthma-like Pathology.
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antagonism of the prostaglandin d2 receptor crth2 attenuates Asthma Pathology in mouse eosinophilic airway inflammation
Respiratory Research, 2007Co-Authors: Lena Uller, Lisa Alenmyr, Magnus Korsgren, Trond Ulven, Thomas Hogberg, Gunnar Andersson, Jesper Mosolff Mathiesen, C Persson, Evi KostenisAbstract:Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic Asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit Asthma-like Pathology. Affinity for and antagonistic potency of TM30089 on many mouse receptors including thromboxane A2 receptor mTP, CRTH2 receptor, and selected anaphylatoxin and chemokines receptors were determined in recombinant expression systems in vitro. In vivo effects of TM30089 and ramatroban on tissue eosinophilia and mucus cell histoPathology were examined in a mouse Asthma model. TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited Asthma Pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia. This is the first report to demonstrate anti-allergic efficacy in vivo of a highly selective small molecule CRTH2 antagonist. Our data suggest that CRTH2 antagonism alone is effective in mouse allergic airway inflammation even to the extent that this mechanism can explain the efficacy of ramatroban.
Stephen J Galli - One of the best experts on this subject based on the ideXlab platform.
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development of multiple features of antigen induced Asthma Pathology in a new strain of mast cell deficient balb c kit w sh w sh mice
Laboratory Investigation, 2020Co-Authors: Joseph D Hernandez, Riccardo Sibilano, Mindy Tsai, Stephen J GalliAbstract:Mast cell-deficient mice are widely used to identify and quantify contributions of mast cells to diverse biological responses in vivo, including allergic inflammation. However, despite the fact that scores of genes have been identified as modifiers of allergic inflammation, most mast cell-deficient models have been available only on a single genetic background. We transferred the KitW-sh allele onto the BALB/c background to generate BALB/c mast cell-deficient mice (BALB/c-KitW-sh/W-sh). BALB/c-KitW-sh/W-sh mice have dramatically reduced mast cell numbers (0–2% of wild type) in all tissues examined, as well as subtle hematologic differences from the corresponding wild type mice, including splenomegaly with evidence of increased splenic hematopoiesis. We examined in BALB/c-KitW-sh/W-sh mice models of allergic inflammation that are substantially diminished in C57BL/6-KitW-sh/W-sh mast cell-deficient mice. In a model of acute allergic inflammation, i.e., IgE-dependent passive cutaneous anaphylaxis, both ear swelling and leukocyte infiltration were largely or entirely absent in BALB/c-KitW-sh/W-sh mice. In contrast, in two different models of allergic airway inflammation, airway hyperresponsiveness, lung inflammation, and airway remodeling developed robustly in mast cell-deficient BALB/c-KitW-sh/W-sh mice. These results support the conclusion that the importance of mast cell contributions in various models of allergic inflammation may be at least partially determined by genetic background. Unlike C57BL/6-KitW-sh/W-sh mice, BALB/c-KitW-sh/W-sh mice exhibit wild-type levels of airway hyperresponsiveness and lung inflammation and remodeling in two models of allergic airway inflammation. By contrast, neither genotype exhibits signs of IgE-dependent passive cutaneous anaphylaxis. Thus, genetic background influences the apparent importance of mast cells in different models of allergic diseases.
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development of multiple features of antigen induced Asthma Pathology in a new strain of mast cell deficient balb c kit w sh w sh mice
Laboratory Investigation, 2020Co-Authors: Joseph D Hernandez, Riccardo Sibilano, Mindy Tsai, Stephen J GalliAbstract:Mast cell-deficient mice are widely used to identify and quantify contributions of mast cells to diverse biological responses in vivo, including allergic inflammation. However, despite the fact that scores of genes have been identified as modifiers of allergic inflammation, most mast cell-deficient models have been available only on a single genetic background. We transferred the KitW-sh allele onto the BALB/c background to generate BALB/c mast cell-deficient mice (BALB/c-KitW-sh/W-sh). BALB/c-KitW-sh/W-sh mice have dramatically reduced mast cell numbers (0-2% of wild type) in all tissues examined, as well as subtle hematologic differences from the corresponding wild type mice, including splenomegaly with evidence of increased splenic hematopoiesis. We examined in BALB/c-KitW-sh/W-sh mice models of allergic inflammation that are substantially diminished in C57BL/6-KitW-sh/W-sh mast cell-deficient mice. In a model of acute allergic inflammation, i.e., IgE-dependent passive cutaneous anaphylaxis, both ear swelling and leukocyte infiltration were largely or entirely absent in BALB/c-KitW-sh/W-sh mice. In contrast, in two different models of allergic airway inflammation, airway hyperresponsiveness, lung inflammation, and airway remodeling developed robustly in mast cell-deficient BALB/c-KitW-sh/W-sh mice. These results support the conclusion that the importance of mast cell contributions in various models of allergic inflammation may be at least partially determined by genetic background.
Lena Uller - One of the best experts on this subject based on the ideXlab platform.
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antagonism of the prostaglandin d2 receptor crth2 attenuates Asthma Pathology in mouse eosinophilic airway inflammation
Respiratory Research, 2007Co-Authors: Lena Uller, Lisa Alenmyr, Magnus Korsgren, Trond Ulven, Thomas Hogberg, Gunnar Andersson, Carl G A Persson, Jesper Mosolff Mathiesen, Evi KostenisAbstract:Background Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic Asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit Asthma-like Pathology.
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antagonism of the prostaglandin d2 receptor crth2 attenuates Asthma Pathology in mouse eosinophilic airway inflammation
Respiratory Research, 2007Co-Authors: Lena Uller, Lisa Alenmyr, Magnus Korsgren, Trond Ulven, Thomas Hogberg, Gunnar Andersson, Jesper Mosolff Mathiesen, C Persson, Evi KostenisAbstract:Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic Asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit Asthma-like Pathology. Affinity for and antagonistic potency of TM30089 on many mouse receptors including thromboxane A2 receptor mTP, CRTH2 receptor, and selected anaphylatoxin and chemokines receptors were determined in recombinant expression systems in vitro. In vivo effects of TM30089 and ramatroban on tissue eosinophilia and mucus cell histoPathology were examined in a mouse Asthma model. TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited Asthma Pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia. This is the first report to demonstrate anti-allergic efficacy in vivo of a highly selective small molecule CRTH2 antagonist. Our data suggest that CRTH2 antagonism alone is effective in mouse allergic airway inflammation even to the extent that this mechanism can explain the efficacy of ramatroban.
Joseph D Hernandez - One of the best experts on this subject based on the ideXlab platform.
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development of multiple features of antigen induced Asthma Pathology in a new strain of mast cell deficient balb c kit w sh w sh mice
Laboratory Investigation, 2020Co-Authors: Joseph D Hernandez, Riccardo Sibilano, Mindy Tsai, Stephen J GalliAbstract:Mast cell-deficient mice are widely used to identify and quantify contributions of mast cells to diverse biological responses in vivo, including allergic inflammation. However, despite the fact that scores of genes have been identified as modifiers of allergic inflammation, most mast cell-deficient models have been available only on a single genetic background. We transferred the KitW-sh allele onto the BALB/c background to generate BALB/c mast cell-deficient mice (BALB/c-KitW-sh/W-sh). BALB/c-KitW-sh/W-sh mice have dramatically reduced mast cell numbers (0–2% of wild type) in all tissues examined, as well as subtle hematologic differences from the corresponding wild type mice, including splenomegaly with evidence of increased splenic hematopoiesis. We examined in BALB/c-KitW-sh/W-sh mice models of allergic inflammation that are substantially diminished in C57BL/6-KitW-sh/W-sh mast cell-deficient mice. In a model of acute allergic inflammation, i.e., IgE-dependent passive cutaneous anaphylaxis, both ear swelling and leukocyte infiltration were largely or entirely absent in BALB/c-KitW-sh/W-sh mice. In contrast, in two different models of allergic airway inflammation, airway hyperresponsiveness, lung inflammation, and airway remodeling developed robustly in mast cell-deficient BALB/c-KitW-sh/W-sh mice. These results support the conclusion that the importance of mast cell contributions in various models of allergic inflammation may be at least partially determined by genetic background. Unlike C57BL/6-KitW-sh/W-sh mice, BALB/c-KitW-sh/W-sh mice exhibit wild-type levels of airway hyperresponsiveness and lung inflammation and remodeling in two models of allergic airway inflammation. By contrast, neither genotype exhibits signs of IgE-dependent passive cutaneous anaphylaxis. Thus, genetic background influences the apparent importance of mast cells in different models of allergic diseases.
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development of multiple features of antigen induced Asthma Pathology in a new strain of mast cell deficient balb c kit w sh w sh mice
Laboratory Investigation, 2020Co-Authors: Joseph D Hernandez, Riccardo Sibilano, Mindy Tsai, Stephen J GalliAbstract:Mast cell-deficient mice are widely used to identify and quantify contributions of mast cells to diverse biological responses in vivo, including allergic inflammation. However, despite the fact that scores of genes have been identified as modifiers of allergic inflammation, most mast cell-deficient models have been available only on a single genetic background. We transferred the KitW-sh allele onto the BALB/c background to generate BALB/c mast cell-deficient mice (BALB/c-KitW-sh/W-sh). BALB/c-KitW-sh/W-sh mice have dramatically reduced mast cell numbers (0-2% of wild type) in all tissues examined, as well as subtle hematologic differences from the corresponding wild type mice, including splenomegaly with evidence of increased splenic hematopoiesis. We examined in BALB/c-KitW-sh/W-sh mice models of allergic inflammation that are substantially diminished in C57BL/6-KitW-sh/W-sh mast cell-deficient mice. In a model of acute allergic inflammation, i.e., IgE-dependent passive cutaneous anaphylaxis, both ear swelling and leukocyte infiltration were largely or entirely absent in BALB/c-KitW-sh/W-sh mice. In contrast, in two different models of allergic airway inflammation, airway hyperresponsiveness, lung inflammation, and airway remodeling developed robustly in mast cell-deficient BALB/c-KitW-sh/W-sh mice. These results support the conclusion that the importance of mast cell contributions in various models of allergic inflammation may be at least partially determined by genetic background.
Lisa Alenmyr - One of the best experts on this subject based on the ideXlab platform.
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antagonism of the prostaglandin d2 receptor crth2 attenuates Asthma Pathology in mouse eosinophilic airway inflammation
Respiratory Research, 2007Co-Authors: Lena Uller, Lisa Alenmyr, Magnus Korsgren, Trond Ulven, Thomas Hogberg, Gunnar Andersson, Carl G A Persson, Jesper Mosolff Mathiesen, Evi KostenisAbstract:Background Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic Asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit Asthma-like Pathology.
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antagonism of the prostaglandin d2 receptor crth2 attenuates Asthma Pathology in mouse eosinophilic airway inflammation
Respiratory Research, 2007Co-Authors: Lena Uller, Lisa Alenmyr, Magnus Korsgren, Trond Ulven, Thomas Hogberg, Gunnar Andersson, Jesper Mosolff Mathiesen, C Persson, Evi KostenisAbstract:Mast cell-derived prostaglandin D2 (PGD2), may contribute to eosinophilic inflammation and mucus production in allergic Asthma. Chemoattractant receptor homologous molecule expressed on TH2 cells (CRTH2), a high affinity receptor for prostaglandin D2, mediates trafficking of TH2-cells, mast cells, and eosinophils to inflammatory sites, and has recently attracted interest as target for treatment of allergic airway diseases. The present study involving mice explores the specificity of CRTH2 antagonism of TM30089, which is structurally closely related to the dual TP/CRTH2 antagonist ramatroban, and compares the ability of ramatroban and TM30089 to inhibit Asthma-like Pathology. Affinity for and antagonistic potency of TM30089 on many mouse receptors including thromboxane A2 receptor mTP, CRTH2 receptor, and selected anaphylatoxin and chemokines receptors were determined in recombinant expression systems in vitro. In vivo effects of TM30089 and ramatroban on tissue eosinophilia and mucus cell histoPathology were examined in a mouse Asthma model. TM30089, displayed high selectivity for and antagonistic potency on mouse CRTH2 but lacked affinity to TP and many other receptors including the related anaphylatoxin C3a and C5a receptors, selected chemokine receptors and the cyclooxygenase isoforms 1 and 2 which are all recognized players in allergic diseases. Furthermore, TM30089 and ramatroban, the latter used as a reference herein, similarly inhibited Asthma Pathology in vivo by reducing peribronchial eosinophilia and mucus cell hyperplasia. This is the first report to demonstrate anti-allergic efficacy in vivo of a highly selective small molecule CRTH2 antagonist. Our data suggest that CRTH2 antagonism alone is effective in mouse allergic airway inflammation even to the extent that this mechanism can explain the efficacy of ramatroban.
