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Glenn T. Furuta - One of the best experts on this subject based on the ideXlab platform.
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Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
Pediatric Research, 2013Co-Authors: Peter D. Ngo, R. John Macleod, Vince Mukkada, Razan Turki, Glenn T. FurutaAbstract:Background: Eosinophils reside in normal gastrointestinal tracts and increase during disease states. Receptors for Eosinophil-derived Granule Proteins (EDGPs) have not been identified, but highly cationic molecules, similar to Eosinophil Proteins, bind extracellular calcium–sensing receptors (CaSRs). We hypothesized that stimulation of CaSRs by Eosinophil Proteins activates epithelial cells. Methods: Caco2 intestinal epithelial cells, AML14.3D10 Eosinophils, wild-type (WT) human embryonic kidney 293 (HEK293) cells not expressing CaSRs (HEK-WT), and CaSR-transfected HEK293 cells (HEK-CaSR) were stimulated with an Eosinophil Protein analog poly- L -arginine (PA) and phosphorylated extracellular signal–regulated kinase (pERK)1 and pERK2 were measured. Functional activation was measured with collagen lattice contraction assays. Results: Coculture of Caco2 cells with AML14.3D10 Eosinophils augmented lattice contraction as compared with lattices containing Caco2 cells alone. PA stimulation of Caco2 lattices augmented contraction. HEK-CaSR stimulation with PA or Ca^2+ resulted in greater pERK activation than that of stimulated HEK-WT cells. PA stimulated greater HEK-CaSR lattice contraction than unstimulated lattices. Contraction of PA-stimulated and PA-unstimulated HEK-WT lattices did not differ. Conclusion: Exposure of intestinal epithelia to the EDGP analog PA stimulates CaSR-dependent ERK phosphorylation and epithelial-mediated collagen lattice contraction. We speculate that EDGP release within the epithelial layers activates the CaSR receptor, leading to matrix contraction and tissue fibrosis.
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epithelial calcium sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
Pediatric Research, 2013Co-Authors: Peter D. Ngo, Vince Mukkada, Razan Turki, John R Macleod, Glenn T. FurutaAbstract:Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
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Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
Pediatric Research, 2012Co-Authors: Peter D. Ngo, R. John Macleod, Vince Mukkada, Razan Turki, Glenn T. FurutaAbstract:Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
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Epithelial calcium-sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction.
Pediatric research, 2012Co-Authors: Peter D. Ngo, R. John Macleod, Vince Mukkada, Razan Turki, Glenn T. FurutaAbstract:Eosinophils reside in normal gastrointestinal tracts and increase during disease states. Receptors for Eosinophil-derived Granule Proteins (EDGPs) have not been identified, but highly cationic molecules, similar to Eosinophil Proteins, bind extracellular calcium-sensing receptors (CaSRs). We hypothesized that stimulation of CaSRs by Eosinophil Proteins activates epithelial cells. Caco2 intestinal epithelial cells, AML14.3D10 Eosinophils, wild-type (WT) human embryonic kidney 293 (HEK293) cells not expressing CaSRs (HEK-WT), and CaSR-transfected HEK293 cells (HEK-CaSR) were stimulated with an Eosinophil Protein analog poly-L-arginine (PA) and phosphorylated extracellular signal-regulated kinase (pERK)1 and pERK2 were measured. Functional activation was measured with collagen lattice contraction assays. Coculture of Caco2 cells with AML14.3D10 Eosinophils augmented lattice contraction as compared with lattices containing Caco2 cells alone. PA stimulation of Caco2 lattices augmented contraction. HEK-CaSR stimulation with PA or Ca(2+) resulted in greater pERK activation than that of stimulated HEK-WT cells. PA stimulated greater HEK-CaSR lattice contraction than unstimulated lattices. Contraction of PA-stimulated and PA-unstimulated HEK-WT lattices did not differ. Exposure of intestinal epithelia to the EDGP analog PA stimulates CaSR-dependent ERK phosphorylation and epithelial-mediated collagen lattice contraction. We speculate that EDGP release within the epithelial layers activates the CaSR receptor, leading to matrix contraction and tissue fibrosis.
Gerald J. Gleich - One of the best experts on this subject based on the ideXlab platform.
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Eosinophil Granule major basic Protein 1 deposition in Eosinophilic esophagitis correlates with symptoms independent of Eosinophil counts
Diseases of The Esophagus, 2019Co-Authors: Kathryn A. Peterson, Gerald J. Gleich, Frederic Clayton, Hedieh Saffari, John C. Fang, N S Limaye, H Crispin, Jacob Robson, Kristin M LeifermanAbstract:In patients with Eosinophilic esophagitis (EoE), symptoms often do not correlate with peak Eosinophil counts (PEC) determined on histopathological examination of biopsy specimens. This may be because Eosinophils degranulate during active disease and lose their morphological identity as intact cells and, therefore, are not enumerated on microscopic examination. Eosinophil Granule Proteins that are released into tissues with degranulation, including major basic Protein 1 (eMBP1), likely contribute to disease pathogenesis and, therefore, may correlate with symptoms better than PEC. We sought to determine whether symptoms in patients with EoE more closely relate to Eosinophil Granule Protein deposition than to Eosinophil enumeration, especially in patients with fewer than 15 Eosinophils per high power field (HPF). Esophageal biopsy specimens from 34 patients diagnosed with EoE were obtained for histopathological examination and for evaluation of eMBP1 staining by indirect immunofluorescence. PEC by histopathology were compared to extracellular eMBP1 grades by immunostaining. PEC and eMBP1 grades also were analyzed for their relationship to symptoms and clinical course. Biopsy specimens from 19 of the 34 patients had fewer than 15 PEC on histopathological examination, and the other 15 patients had 15 or greater PEC. Positive eMBP1 immunostaining was found in all symptomatic patients. EoE symptoms were related to eMBP1 immunostaining grades (p = 0.0001), but not PEC (P = 0.14). Eosinophil Granule Protein deposition, specifically eMBP1, is increased in esophageal biopsy specimens from symptomatic patients with EoE and may be a marker of disease activity, including patients with EoE who have 'resolved' disease.
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Extracellular Eosinophil Granule Protein Deposition in Ringed Esophagus with Sparse Eosinophils
Digestive diseases and sciences, 2015Co-Authors: Kathryn A. Peterson, William J. Cobell, Frederic Clayton, Chaya Krishnamurthy, Jian Ying, Leonard F. Pease, Hedieh Saffari, Ann Georgelas, John C. Fang, Gerald J. GleichAbstract:Background Eosinophilic esophagitis (EoE) remains difficult to classify because of varying presentations. Not uncommonly, patients present with symptoms of esophageal dysfunction and have esophageal changes on endoscopy resembling EoE but without[15 Eosinophils/HPF. Patients with low numbers of Eosinophils in esophageal biopsy specimens may have esophageal changes and symptomatic disease brought about by Eosinophil Granule Protein deposition without recognizable intact cells. Aim To determine whether extracellular Eosinophil Granule Protein deposition is present in the esophagi of patients with low Eosinophil numbers who have clinical symptoms and characteristic endoscopic esophageal changes of EoE including ringed esophagus (RE). Methods Esophageal biopsy specimens were studied from eight EoE patients with[15 Eosinophils per high power field (HPF) and nine patients with RE (\15 Eosinophils/HPF). The specimens were analyzed for Eosinophil Granule Proteins, major basic Protein 1 (eMBP1) and Eosinophil-derived neurotoxin (EDN), by indirect immunofluorescence. Results Both EoE and RE showed positive EDN and eMBP1 extracellular deposition; control esophagus showed minimal or none. Comparing EoE and RE, extracellular EDN and eMBP1 were similar except that EDN in EoE was greater in the distal esophagus. Conclusions This study highlights the importance of assessing Eosinophil Granule Protein deposition in esophageal disease with potential Eosinophil involvement. Persistent/progressive esophageal changes may be brought about by Eosinophil Granule Proteins despite low numbers of intact cells. The meaning of ‘‘resolution’’ in EoE may need to be redefined based on numbers of esophageal Eosinophils, extracellular Eosinophil Granule Protein deposition, and subsequent clinical course of patients.
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Eosinophil Granule Protein localization in Eosinophilic endomyocardial disease.
The New England journal of medicine, 2011Co-Authors: Benjamin L. Wright, Kristin M Leiferman, Gerald J. GleichAbstract:In this case report, Eosinophilic endomyocardial disease was diagnosed in a patient on the basis of immunohistochemical evidence of Eosinophil Granule Protein deposition in the heart, even in the absence of Eosinophilic infiltration on cardiac biopsy.
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Mechanism of sphingosine 1-phosphate- and lysophosphatidic acid-induced up-regulation of adhesion molecules and Eosinophil chemoattractant in nerve cells.
International journal of molecular sciences, 2011Co-Authors: Richard W. Costello, Gerald J. Gleich, Michael Maloney, Mazin Atiyeh, Marie Therese WalshAbstract:The lysophospholipids sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) act via G-Protein coupled receptors S1P1–5 and LPA1–3 respectively, and are implicated in allergy. Eosinophils accumulate at innervating cholinergic nerves in asthma and adhere to nerve cells via intercellular adhesion molecule-1 (ICAM-1). IMR-32 neuroblastoma cells were used as an in vitro cholinergic nerve cell model. The Gi coupled receptors S1P1, S1P3, LPA1, LPA2 and LPA3 were expressed on IMR-32 cells. Both S1P and LPA induced ERK phosphorylation and ERK- and Gi-dependent up-regulation of ICAM-1 expression, with differing time courses. LPA also induced ERK- and Gi-dependent up-regulation of the Eosinophil chemoattractant, CCL-26. The Eosinophil Granule Protein Eosinophil peroxidase (EPO) induced ERK-dependent up-regulation of transcription of S1P1, LPA1, LPA2 and LPA3, providing the situation whereby Eosinophil Granule Proteins may enhance S1P- and/or LPA- induced Eosinophil accumulation at nerve cells in allergic conditions.
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EGO, a novel, noncoding RNA gene, regulates Eosinophil Granule Protein transcript expression.
Blood, 2007Co-Authors: Lori A. Wagner, Ann Georgelas, Clarissa Christensen, Diane M. Dunn, Gerald J. Spangrude, Linda L. Kelley, M. Sean Esplin, Robert B. Weiss, Gerald J. GleichAbstract:Gene expression profiling of early Eosinophil development shows increased transcript levels of proinflammatory cytokines, chemokines, transcription factors, and a novel gene, EGO (Eosinophil Granule ontogeny). EGO is nested within an intron of the inositol triphosphate receptor type 1 (ITPR1) gene and is conserved at the nucleotide level; however, the largest open reading frame (ORF) is 86 amino acids. Sucrose density gradients show that EGO is not associated with ribosomes and therefore is a noncoding RNA (ncRNA). EGO transcript levels rapidly increase following interleukin-5 (IL-5) stimulation of CD34+ hematopoietic progenitors. EGO RNA also is highly expressed in human bone marrow and in mature Eosinophils. RNA silencing of EGO results in decreased major basic Protein (MBP) and Eosinophil derived neurotoxin (EDN) mRNA expression in developing CD34+ hematopoietic progenitors in vitro and in a CD34+ cell line model. Therefore, EGO is a novel ncRNA gene expressed during Eosinophil development and is necessary for normal MBP and EDN transcript expression.
Peter D. Ngo - One of the best experts on this subject based on the ideXlab platform.
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Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
Pediatric Research, 2013Co-Authors: Peter D. Ngo, R. John Macleod, Vince Mukkada, Razan Turki, Glenn T. FurutaAbstract:Background: Eosinophils reside in normal gastrointestinal tracts and increase during disease states. Receptors for Eosinophil-derived Granule Proteins (EDGPs) have not been identified, but highly cationic molecules, similar to Eosinophil Proteins, bind extracellular calcium–sensing receptors (CaSRs). We hypothesized that stimulation of CaSRs by Eosinophil Proteins activates epithelial cells. Methods: Caco2 intestinal epithelial cells, AML14.3D10 Eosinophils, wild-type (WT) human embryonic kidney 293 (HEK293) cells not expressing CaSRs (HEK-WT), and CaSR-transfected HEK293 cells (HEK-CaSR) were stimulated with an Eosinophil Protein analog poly- L -arginine (PA) and phosphorylated extracellular signal–regulated kinase (pERK)1 and pERK2 were measured. Functional activation was measured with collagen lattice contraction assays. Results: Coculture of Caco2 cells with AML14.3D10 Eosinophils augmented lattice contraction as compared with lattices containing Caco2 cells alone. PA stimulation of Caco2 lattices augmented contraction. HEK-CaSR stimulation with PA or Ca^2+ resulted in greater pERK activation than that of stimulated HEK-WT cells. PA stimulated greater HEK-CaSR lattice contraction than unstimulated lattices. Contraction of PA-stimulated and PA-unstimulated HEK-WT lattices did not differ. Conclusion: Exposure of intestinal epithelia to the EDGP analog PA stimulates CaSR-dependent ERK phosphorylation and epithelial-mediated collagen lattice contraction. We speculate that EDGP release within the epithelial layers activates the CaSR receptor, leading to matrix contraction and tissue fibrosis.
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epithelial calcium sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
Pediatric Research, 2013Co-Authors: Peter D. Ngo, Vince Mukkada, Razan Turki, John R Macleod, Glenn T. FurutaAbstract:Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
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Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
Pediatric Research, 2012Co-Authors: Peter D. Ngo, R. John Macleod, Vince Mukkada, Razan Turki, Glenn T. FurutaAbstract:Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
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Epithelial calcium-sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction.
Pediatric research, 2012Co-Authors: Peter D. Ngo, R. John Macleod, Vince Mukkada, Razan Turki, Glenn T. FurutaAbstract:Eosinophils reside in normal gastrointestinal tracts and increase during disease states. Receptors for Eosinophil-derived Granule Proteins (EDGPs) have not been identified, but highly cationic molecules, similar to Eosinophil Proteins, bind extracellular calcium-sensing receptors (CaSRs). We hypothesized that stimulation of CaSRs by Eosinophil Proteins activates epithelial cells. Caco2 intestinal epithelial cells, AML14.3D10 Eosinophils, wild-type (WT) human embryonic kidney 293 (HEK293) cells not expressing CaSRs (HEK-WT), and CaSR-transfected HEK293 cells (HEK-CaSR) were stimulated with an Eosinophil Protein analog poly-L-arginine (PA) and phosphorylated extracellular signal-regulated kinase (pERK)1 and pERK2 were measured. Functional activation was measured with collagen lattice contraction assays. Coculture of Caco2 cells with AML14.3D10 Eosinophils augmented lattice contraction as compared with lattices containing Caco2 cells alone. PA stimulation of Caco2 lattices augmented contraction. HEK-CaSR stimulation with PA or Ca(2+) resulted in greater pERK activation than that of stimulated HEK-WT cells. PA stimulated greater HEK-CaSR lattice contraction than unstimulated lattices. Contraction of PA-stimulated and PA-unstimulated HEK-WT lattices did not differ. Exposure of intestinal epithelia to the EDGP analog PA stimulates CaSR-dependent ERK phosphorylation and epithelial-mediated collagen lattice contraction. We speculate that EDGP release within the epithelial layers activates the CaSR receptor, leading to matrix contraction and tissue fibrosis.
Simon A. Lewis - One of the best experts on this subject based on the ideXlab platform.
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Eosinophil major basic Protein increases membrane permeability in mammalian urinary bladder epithelium
American Journal of Physiology-cell Physiology, 1998Co-Authors: Teri J. Kleine, Gerald J. Gleich, Simon A. LewisAbstract:The Eosinophil Granule Protein major basic Protein (MBP) is toxic to a wide variety of cell types, by a poorly understood mechanism. To determine whether the action of MBP involves an alteration in membrane permeability, we tested purified MBP on rabbit urinary bladder epithelium using transepithelial voltage-clamp techniques. Addition of nanomolar concentrations of MBP to the mucosal solution caused an increase in apical membrane conductance only when the voltage across the apical membrane was cell interior negative. The magnitude of the MBP-induced conductance was a function of MBP concentration, and the rate of the initial increase in conductance was a function of the transepithelial voltage. The MBP-induced conductance was nonselective for K+ and Cl−. Mucosal Ca2+ reversed the induced conductance, whereas mucosal Mg2+partially blocked the induced conductance and slowed the rate of the increase in conductance. The induced conductance was partially reversed by changing the voltage gradient across the ap...
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Eosinophil major basic Protein increases membrane permeability in mammalian urinary bladder epithelium
American Journal of Physiology-cell Physiology, 1998Co-Authors: Teri J. Kleine, Gerald J. Gleich, Simon A. LewisAbstract:The Eosinophil Granule Protein major basic Protein (MBP) is toxic to a wide variety of cell types, by a poorly understood mechanism. To determine whether the action of MBP involves an alteration in...
Razan Turki - One of the best experts on this subject based on the ideXlab platform.
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Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
Pediatric Research, 2013Co-Authors: Peter D. Ngo, R. John Macleod, Vince Mukkada, Razan Turki, Glenn T. FurutaAbstract:Background: Eosinophils reside in normal gastrointestinal tracts and increase during disease states. Receptors for Eosinophil-derived Granule Proteins (EDGPs) have not been identified, but highly cationic molecules, similar to Eosinophil Proteins, bind extracellular calcium–sensing receptors (CaSRs). We hypothesized that stimulation of CaSRs by Eosinophil Proteins activates epithelial cells. Methods: Caco2 intestinal epithelial cells, AML14.3D10 Eosinophils, wild-type (WT) human embryonic kidney 293 (HEK293) cells not expressing CaSRs (HEK-WT), and CaSR-transfected HEK293 cells (HEK-CaSR) were stimulated with an Eosinophil Protein analog poly- L -arginine (PA) and phosphorylated extracellular signal–regulated kinase (pERK)1 and pERK2 were measured. Functional activation was measured with collagen lattice contraction assays. Results: Coculture of Caco2 cells with AML14.3D10 Eosinophils augmented lattice contraction as compared with lattices containing Caco2 cells alone. PA stimulation of Caco2 lattices augmented contraction. HEK-CaSR stimulation with PA or Ca^2+ resulted in greater pERK activation than that of stimulated HEK-WT cells. PA stimulated greater HEK-CaSR lattice contraction than unstimulated lattices. Contraction of PA-stimulated and PA-unstimulated HEK-WT lattices did not differ. Conclusion: Exposure of intestinal epithelia to the EDGP analog PA stimulates CaSR-dependent ERK phosphorylation and epithelial-mediated collagen lattice contraction. We speculate that EDGP release within the epithelial layers activates the CaSR receptor, leading to matrix contraction and tissue fibrosis.
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epithelial calcium sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
Pediatric Research, 2013Co-Authors: Peter D. Ngo, Vince Mukkada, Razan Turki, John R Macleod, Glenn T. FurutaAbstract:Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
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Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
Pediatric Research, 2012Co-Authors: Peter D. Ngo, R. John Macleod, Vince Mukkada, Razan Turki, Glenn T. FurutaAbstract:Epithelial calcium–sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction
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Epithelial calcium-sensing receptor activation by Eosinophil Granule Protein analog stimulates collagen matrix contraction.
Pediatric research, 2012Co-Authors: Peter D. Ngo, R. John Macleod, Vince Mukkada, Razan Turki, Glenn T. FurutaAbstract:Eosinophils reside in normal gastrointestinal tracts and increase during disease states. Receptors for Eosinophil-derived Granule Proteins (EDGPs) have not been identified, but highly cationic molecules, similar to Eosinophil Proteins, bind extracellular calcium-sensing receptors (CaSRs). We hypothesized that stimulation of CaSRs by Eosinophil Proteins activates epithelial cells. Caco2 intestinal epithelial cells, AML14.3D10 Eosinophils, wild-type (WT) human embryonic kidney 293 (HEK293) cells not expressing CaSRs (HEK-WT), and CaSR-transfected HEK293 cells (HEK-CaSR) were stimulated with an Eosinophil Protein analog poly-L-arginine (PA) and phosphorylated extracellular signal-regulated kinase (pERK)1 and pERK2 were measured. Functional activation was measured with collagen lattice contraction assays. Coculture of Caco2 cells with AML14.3D10 Eosinophils augmented lattice contraction as compared with lattices containing Caco2 cells alone. PA stimulation of Caco2 lattices augmented contraction. HEK-CaSR stimulation with PA or Ca(2+) resulted in greater pERK activation than that of stimulated HEK-WT cells. PA stimulated greater HEK-CaSR lattice contraction than unstimulated lattices. Contraction of PA-stimulated and PA-unstimulated HEK-WT lattices did not differ. Exposure of intestinal epithelia to the EDGP analog PA stimulates CaSR-dependent ERK phosphorylation and epithelial-mediated collagen lattice contraction. We speculate that EDGP release within the epithelial layers activates the CaSR receptor, leading to matrix contraction and tissue fibrosis.