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Armin Braun - One of the best experts on this subject based on the ideXlab platform.
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The contribution of Neurotrophins to the pathogenesis of allergic asthma.
Biochemical Society Transactions, 2006Co-Authors: Sabine Rochlitzer, Christina Nassenstein, Armin BraunAbstract:The Neurotrophins nerve growth factor, brain-derived neurotrophic factor, NT-3 (neurotrophin 3) and NT-4 are known for regulating neuron development, function and survival. Beyond this, Neurotrophins were found to exert multiple effects on non-neuronal cells such as immune cells, smooth muscle and epithelial cells. In allergic asthma, airway inflammation, airway obstruction, AHR (airway hyperresponsiveness) and airway remodelling are characteristic features, indicating an intensive interaction between neuronal, structural and immune cells in the lung. In allergic asthma patients, elevated neurotrophin levels in the blood and locally in the lung are commonly observed. Additionally, structural cells of the lung and immune cells, present in the lung during airway inflammation, were shown to be capable of neurotrophin production. A functional relationship between Neurotrophins and the main features of asthma was revealed, as airway obstruction, airway inflammation, AHR and airway remodelling were all shown to be stimulated by Neurotrophins. The aim of the present review is to provide an overview of neurotrophin sources and target cells in the lung, concerning their possible role as mediators between structural cells, immune cells and neurons, connecting the different features of allergic asthma.
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Neurotrophins and neurotrophin receptors in allergic asthma.
Progress in Brain Research, 2004Co-Authors: Christina Nassenstein, Sebastian Kerzel, Armin BraunAbstract:The Neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NT-3) and NT-4 play a pivotal role in the development of the nervous system. Despite their well-known effects on neurons, elevated neurotrophin concentrations have been observed under pathological conditions in sera of patients with inflammatory disorders. Patients with asthma feature both airway inflammation and an abnormal airway reactivity to many unspecific stimuli, referred to as airway hyperresponsiveness, which is, at least partly, neuronally controlled. Interestingly, these patients show increased levels of Neurotrophins in the blood as well as locally in the lung. It has been demonstrated that neurotrophin release from immune cells is triggered by allergen contact. The presence of Neurotrophins and the neurotrophin receptors p75 (p75NTR), tyrosine kinase A (TrkA), TrkB and TrkC have been described in several immune cells. There is strong evidence for an involvement of Neurotrophins in regulation of hematopoiesis and, in addition, in modulation of immune cell function in mature cells circulating in blood or resting in lymphatic organs and peripheral tissues. The aim of this review is to demonstrate possible roles of Neurotrophins during an allergic reaction in consideration of the temporospatial compartimentalization.
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the Neurotrophins nerve growth factor brain derived neurotrophic factor neurotrophin 3 and neurotrophin 4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma
Journal of Experimental Medicine, 2003Co-Authors: Christina Nassenstein, Werner Luttmann, Armin Braun, Marek Lommatzsch, Stephanie Schmidt, Veit J. Erpenbeck, Norbert Krug, Harald Renz, J Christian VirchowAbstract:Neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and NT-4) have been observed in elevated concentrations in allergic diseases. Neurotrophin levels are up-regulated endobronchially after allergen challenge. This coincides with an influx of activated eosinophils into the bronchial lumen. These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood. To investigate whether these observations are related we studied the influence of Neurotrophins on eosinophil function in allergic asthma. Incubation with NGF, BDNF, NT-3, or NT-4 caused a significant increase in the viability and CD69 expression of isolated eosinophils from bronchoalveolar lavage fluid (BALF) but not from peripheral blood, suggesting a unique sensitivity of endobronchial eosinophils to Neurotrophins. To elucidate the underlying mechanisms expression of the neurotrophin receptors p75NTR, trkA, trkB, and trkC on eosinophils was analyzed by RT-PCR and immunocytology. After SAP expression of all neurotrophin receptors was markedly elevated on eosinophils from BALF. Our findings suggest that neurotrophin-mediated activation of bronchial eosinophils might play a role in the regulation of eosinophilic inflammation in allergic asthma.
Sture Forsgren - One of the best experts on this subject based on the ideXlab platform.
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Are Neurotrophins important in ulcerative colitis
Annals of the New York Academy of Sciences, 2007Co-Authors: Malin Johansson, Örjan Norrgård, Sture ForsgrenAbstract:Neurotrophins are known to have growth, survival-promoting, and healing effects. The importance of Neurotrophins in ulcerative colitis (UC) is, however, unclear. Recent studies in our group revealed that an occurrence of marked changes in neurotrophin expression patterns was related to a worsening of the disease process. There was thus an upregulation for the lamina propria cells but a downregulation in nerve structures concerning neurotrophin expressions in severe UC. The observations show that changes in the neurotrophin system are a part of the disease process in UC and are of interest as treatments interfering with neurotrophin effects in other situations have been found to have trophic and healing effects.
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Study of expression patterns and levels of Neurotrophins and neurotrophin receptors in ulcerative colitis.
Inflammatory Bowel Diseases, 2007Co-Authors: Malin Johansson, Örjan Norrgård, Sture ForsgrenAbstract:Background: Neurotrophins may be involved in ulcerative colitis (UC). Yet, it is unclear whether if their effects should be blocked. Methods: In this study, the Neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors were examined by immunohistochemistry, ELISA, and RT-PCR. Results: BDNF immunoreaction was detected in nerve structures in particular, and NGF immunoreaction was detected in lamina propria cells. Cellular NGF immunoreaction was generally observed to be higher in the mucosa of UC patients than in the controls. In addition, UC patients demonstrated significantly higher p75 immunoreaction (P = 0.010) in lamina propria cells. The controls expressed significantly higher BDNF immunoreaction in the nerve structures than did UC patients (P = 0.000). However, the UC group showed marked interindividual variation in expression of Neurotrophins and neurotrophin receptors. This included variation at the mRNA level for NGF. Differences with the controls were most pronounced in UC specimens demonstrating great infiltration of inflammatory cells and marked tissue derangement. Corticosteroid treatment seemed to affect neurotrophin production in lamina propria cells but not in nerve structures. These observations demonstrate that up-regulation and down-regulation of Neurotrophins occur in different structural components in response to the disease process. Massive inflammation seemed to be correlated with decreased neurotrophin immunoreaction in nerve structures, but there was a tendency toward increased neurotrophin production in lamina propria cells. Conclusions: Our study shows that UC patients are not a uniform group in their expression of Neurotrophins, a fact that should be considered when discussing therapeutic interventions.
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Study of expression patterns and levels of Neurotrophins and neurotrophin receptors in ulcerative colitis.
Inflammatory Bowel Diseases, 2007Co-Authors: Malin Johansson, Örjan Norrgård, Sture ForsgrenAbstract:Background: Neurotrophins may be involved in ulcerative colitis (UC). Yet, it is unclear whether if their effects should be blocked. Methods: In this study, the Neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors were examined by immunohistochemistry, ELISA, and RT-PCR. Results: BDNF immunoreaction was detected in nerve structures in particular, and NGF immunoreaction was detected in lamina propria cells. Cellular NGF immunoreaction was generally observed to be higher in the mucosa of UC patients than in the controls. In addition, UC patients demonstrated significantly higher p75 immunoreaction (P = 0.010) in lamina propria cells. The controls expressed significantly higher BDNF immunoreaction in the nerve structures than did UC patients (P = 0.000). However, the UC group showed marked interindividual variation in expression of Neurotrophins and neurotrophin receptors. This included variation at the mRNA level for NGF. Differences with the controls were most pronounced in UC specimens demonstrating great infiltration of inflammatory cells and marked tissue derangement. Corticosteroid treatment seemed to affect neurotrophin production in lamina propria cells but not in nerve structures. These observations demonstrate that up-regulation and down-regulation of Neurotrophins occur in different structural components in response to the disease process. Massive inflammation seemed to be correlated with decreased neurotrophin immunoreaction in nerve structures, but there was a tendency toward increased neurotrophin production in lamina propria cells. Conclusions: Our study shows that UC patients are not a uniform group in their expression of Neurotrophins, a fact that should be considered when discussing therapeutic interventions.
Eric M Shooter - One of the best experts on this subject based on the ideXlab platform.
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p75 reduces TrkB tyrosine autophosphorylation in response to brain-derived neurotrophic factor and neurotrophin 4/5.
Journal of Biological Chemistry, 2000Co-Authors: Jouni Vesa, Alex Krüttgen, Eric M ShooterAbstract:Abstract Neurotrophins mediate their signals through two different receptors: the family of receptor tyrosine kinases, Trks, and the low affinity pan-neurotrophin receptor p75. Trk receptors show more restricted ligand specificity, whereas all Neurotrophins are able to bind to p75. One important function of p75 is the enhancement of nerve growth factor signaling via TrkA by increasing TrkA tyrosine autophosphorylation. Here, we have examined the importance of p75 on TrkB- and TrkC-mediated neurotrophin signaling in an MG87 fibroblast cell line stably transfected with either p75 and TrkB or p75 and TrkC, as well as in PC12 cells stably transfected with TrkB. In contrast to TrkA signaling, p75 had a negative effect on TrkB tyrosine autophosphorylation in response to its cognate Neurotrophins, brain-derived neurotrophic factor and neurotrophin 4/5. On the other hand, p75 had no effect on TrkB or TrkC activation in neurotrophin 3 treatment. p75 did not effect extracellular signal-regulated kinase 2 tyrosine phosphorylation in response to brain-derived neurotrophic factor, neurotrophin 3, or neurotrophin 4/5. These results suggest that the observed reduction in TrkB tyrosine autophosphorylation caused by p75 does not influence Ras/mitogen-activated protein kinase signaling pathway in neurotrophin treatments.
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Neurotrophins induce release of Neurotrophins by the regulated secretory pathway
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Alex Krüttgen, J. Carsten Möller, John Victor Heymach, Eric M ShooterAbstract:Recent studies have established that neurotrophin synthesis and secretion are regulated by activity and that these factors are involved in activity-dependent processes in the nervous system. Neurotrophins also are known to induce increases in intracellular calcium, a trigger for regulated secretion. This finding raises the possibility that Neurotrophins themselves may stimulate regulated secretion of Neurotrophins. To address this question, we studied the release of Neurotrophins from transfected PC12 cells, a widely used model for neuronal secretion and neurotrophin signal transduction. We found that Neurotrophins induced the regulated secretion of brain-derived neurotrophic factor, neurotrophin-3 (NT-3), and neurotrophin-4/5. The effect of brain-derived neurotrophic factor on release of NT-3 could be abolished by REX, a p75 blocking antibody, but not by K252a, an inhibitor of neurotrophin tyrosine kinase receptor (Trk) signaling. The nerve growth factor effect on release of NT-3 could be blocked only by simultaneous application of REX and K252a, suggesting that they are mediated by TrkA as well as p75. Our data show that Neurotrophins are able to induce the regulated secretion of Neurotrophins and suggest a signal-transducing role for both TrkA and p75 in this process. The neurotrophin-induced release of Neurotrophins may be relevant for activity-dependent processes such as synaptic plasticity and memory formation.
Christina Nassenstein - One of the best experts on this subject based on the ideXlab platform.
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The contribution of Neurotrophins to the pathogenesis of allergic asthma.
Biochemical Society Transactions, 2006Co-Authors: Sabine Rochlitzer, Christina Nassenstein, Armin BraunAbstract:The Neurotrophins nerve growth factor, brain-derived neurotrophic factor, NT-3 (neurotrophin 3) and NT-4 are known for regulating neuron development, function and survival. Beyond this, Neurotrophins were found to exert multiple effects on non-neuronal cells such as immune cells, smooth muscle and epithelial cells. In allergic asthma, airway inflammation, airway obstruction, AHR (airway hyperresponsiveness) and airway remodelling are characteristic features, indicating an intensive interaction between neuronal, structural and immune cells in the lung. In allergic asthma patients, elevated neurotrophin levels in the blood and locally in the lung are commonly observed. Additionally, structural cells of the lung and immune cells, present in the lung during airway inflammation, were shown to be capable of neurotrophin production. A functional relationship between Neurotrophins and the main features of asthma was revealed, as airway obstruction, airway inflammation, AHR and airway remodelling were all shown to be stimulated by Neurotrophins. The aim of the present review is to provide an overview of neurotrophin sources and target cells in the lung, concerning their possible role as mediators between structural cells, immune cells and neurons, connecting the different features of allergic asthma.
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Neurotrophins and neurotrophin receptors in allergic asthma.
Progress in Brain Research, 2004Co-Authors: Christina Nassenstein, Sebastian Kerzel, Armin BraunAbstract:The Neurotrophins nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NT-3) and NT-4 play a pivotal role in the development of the nervous system. Despite their well-known effects on neurons, elevated neurotrophin concentrations have been observed under pathological conditions in sera of patients with inflammatory disorders. Patients with asthma feature both airway inflammation and an abnormal airway reactivity to many unspecific stimuli, referred to as airway hyperresponsiveness, which is, at least partly, neuronally controlled. Interestingly, these patients show increased levels of Neurotrophins in the blood as well as locally in the lung. It has been demonstrated that neurotrophin release from immune cells is triggered by allergen contact. The presence of Neurotrophins and the neurotrophin receptors p75 (p75NTR), tyrosine kinase A (TrkA), TrkB and TrkC have been described in several immune cells. There is strong evidence for an involvement of Neurotrophins in regulation of hematopoiesis and, in addition, in modulation of immune cell function in mature cells circulating in blood or resting in lymphatic organs and peripheral tissues. The aim of this review is to demonstrate possible roles of Neurotrophins during an allergic reaction in consideration of the temporospatial compartimentalization.
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the Neurotrophins nerve growth factor brain derived neurotrophic factor neurotrophin 3 and neurotrophin 4 are survival and activation factors for eosinophils in patients with allergic bronchial asthma
Journal of Experimental Medicine, 2003Co-Authors: Christina Nassenstein, Werner Luttmann, Armin Braun, Marek Lommatzsch, Stephanie Schmidt, Veit J. Erpenbeck, Norbert Krug, Harald Renz, J Christian VirchowAbstract:Neurotrophins (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], neurotrophin [NT]-3, and NT-4) have been observed in elevated concentrations in allergic diseases. Neurotrophin levels are up-regulated endobronchially after allergen challenge. This coincides with an influx of activated eosinophils into the bronchial lumen. These eosinophils have an increased viability and CD69 expression 18 h after segmental allergen provocation (SAP) which is not present in peripheral blood. To investigate whether these observations are related we studied the influence of Neurotrophins on eosinophil function in allergic asthma. Incubation with NGF, BDNF, NT-3, or NT-4 caused a significant increase in the viability and CD69 expression of isolated eosinophils from bronchoalveolar lavage fluid (BALF) but not from peripheral blood, suggesting a unique sensitivity of endobronchial eosinophils to Neurotrophins. To elucidate the underlying mechanisms expression of the neurotrophin receptors p75NTR, trkA, trkB, and trkC on eosinophils was analyzed by RT-PCR and immunocytology. After SAP expression of all neurotrophin receptors was markedly elevated on eosinophils from BALF. Our findings suggest that neurotrophin-mediated activation of bronchial eosinophils might play a role in the regulation of eosinophilic inflammation in allergic asthma.
Malin Johansson - One of the best experts on this subject based on the ideXlab platform.
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Are Neurotrophins important in ulcerative colitis
Annals of the New York Academy of Sciences, 2007Co-Authors: Malin Johansson, Örjan Norrgård, Sture ForsgrenAbstract:Neurotrophins are known to have growth, survival-promoting, and healing effects. The importance of Neurotrophins in ulcerative colitis (UC) is, however, unclear. Recent studies in our group revealed that an occurrence of marked changes in neurotrophin expression patterns was related to a worsening of the disease process. There was thus an upregulation for the lamina propria cells but a downregulation in nerve structures concerning neurotrophin expressions in severe UC. The observations show that changes in the neurotrophin system are a part of the disease process in UC and are of interest as treatments interfering with neurotrophin effects in other situations have been found to have trophic and healing effects.
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Study of expression patterns and levels of Neurotrophins and neurotrophin receptors in ulcerative colitis.
Inflammatory Bowel Diseases, 2007Co-Authors: Malin Johansson, Örjan Norrgård, Sture ForsgrenAbstract:Background: Neurotrophins may be involved in ulcerative colitis (UC). Yet, it is unclear whether if their effects should be blocked. Methods: In this study, the Neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors were examined by immunohistochemistry, ELISA, and RT-PCR. Results: BDNF immunoreaction was detected in nerve structures in particular, and NGF immunoreaction was detected in lamina propria cells. Cellular NGF immunoreaction was generally observed to be higher in the mucosa of UC patients than in the controls. In addition, UC patients demonstrated significantly higher p75 immunoreaction (P = 0.010) in lamina propria cells. The controls expressed significantly higher BDNF immunoreaction in the nerve structures than did UC patients (P = 0.000). However, the UC group showed marked interindividual variation in expression of Neurotrophins and neurotrophin receptors. This included variation at the mRNA level for NGF. Differences with the controls were most pronounced in UC specimens demonstrating great infiltration of inflammatory cells and marked tissue derangement. Corticosteroid treatment seemed to affect neurotrophin production in lamina propria cells but not in nerve structures. These observations demonstrate that up-regulation and down-regulation of Neurotrophins occur in different structural components in response to the disease process. Massive inflammation seemed to be correlated with decreased neurotrophin immunoreaction in nerve structures, but there was a tendency toward increased neurotrophin production in lamina propria cells. Conclusions: Our study shows that UC patients are not a uniform group in their expression of Neurotrophins, a fact that should be considered when discussing therapeutic interventions.
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Study of expression patterns and levels of Neurotrophins and neurotrophin receptors in ulcerative colitis.
Inflammatory Bowel Diseases, 2007Co-Authors: Malin Johansson, Örjan Norrgård, Sture ForsgrenAbstract:Background: Neurotrophins may be involved in ulcerative colitis (UC). Yet, it is unclear whether if their effects should be blocked. Methods: In this study, the Neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and their receptors were examined by immunohistochemistry, ELISA, and RT-PCR. Results: BDNF immunoreaction was detected in nerve structures in particular, and NGF immunoreaction was detected in lamina propria cells. Cellular NGF immunoreaction was generally observed to be higher in the mucosa of UC patients than in the controls. In addition, UC patients demonstrated significantly higher p75 immunoreaction (P = 0.010) in lamina propria cells. The controls expressed significantly higher BDNF immunoreaction in the nerve structures than did UC patients (P = 0.000). However, the UC group showed marked interindividual variation in expression of Neurotrophins and neurotrophin receptors. This included variation at the mRNA level for NGF. Differences with the controls were most pronounced in UC specimens demonstrating great infiltration of inflammatory cells and marked tissue derangement. Corticosteroid treatment seemed to affect neurotrophin production in lamina propria cells but not in nerve structures. These observations demonstrate that up-regulation and down-regulation of Neurotrophins occur in different structural components in response to the disease process. Massive inflammation seemed to be correlated with decreased neurotrophin immunoreaction in nerve structures, but there was a tendency toward increased neurotrophin production in lamina propria cells. Conclusions: Our study shows that UC patients are not a uniform group in their expression of Neurotrophins, a fact that should be considered when discussing therapeutic interventions.