Altered expression of epithelial junctional proteins in atopic asthma: possible role in inflammation
Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the epithelium....
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Published in | Canadian journal of physiology and pharmacology Vol. 86; no. 3; pp. 105 - 112 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Ottawa, ON
National Research Council of Canada
01.03.2008
NRC Research Press Canadian Science Publishing NRC Research Press |
Subjects | |
Online Access | Get full text |
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Abstract | Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the epithelium. Bronchial epithelial fragility has been reported in asthmatic patients, but little is known about the expression of TJ and AJ proteins in asthma. We studied epithelial expression of zonula occludens-1 (ZO-1) and AJ proteins E-cadherin, α-catenin, and β-catenin in bronchial biopsies from nonatopic nonasthmatic (healthy) subjects (n = 14), and stable atopic asthmatic subjects (n = 22) at baseline conditions. Immunostaining for these proteins was semi-quantified for separate cellular compartments. E-cadherin, α-catenin and β-catenin were present in the cellular membrane and less in the cytoplasm. Only β-catenin was present in the nucleus in agreement with its potential function as transcription factor. ZO-1 was present in the apicolateral membrane of superficial cells. α-Catenin expression was significantly lower in subjects with asthma than without and correlated inversely with numbers of eosinophils within the epithelium. ZO-1 and E-cadherin expression were significantly lower in asthmatic than in nonasthmatic subjects. Expression of β-catenin was not different. Our results suggest that the lower epithelial α-catenin, E-cadherin and (or) ZO-1 expression in patients with atopic asthma contributes to a defective airway epithelial barrier and a higher influx of eosinophils in the epithelium. |
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AbstractList | Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the epithelium. Bronchial epithelial fragility has been reported in asthmatic patients, but little is known about the expression of TJ and AJ proteins in asthma. We studied epithelial expression of zonula occludens-1 (ZO-1) and AJ proteins E-cadherin, alpha-catenin, and beta-catenin in bronchial biopsies from nonatopic nonasthmatic (healthy) subjects (n = 14), and stable atopic asthmatic subjects (n = 22) at baseline conditions. Immunostaining for these proteins was semi-quantified for separate cellular compartments. E-cadherin, alpha-catenin and beta-catenin were present in the cellular membrane and less in the cytoplasm. Only beta-catenin was present in the nucleus in agreement with its potential function as transcription factor. ZO-1 was present in the apicolateral membrane of superficial cells. alpha-Catenin expression was significantly lower in subjects with asthma than without and correlated inversely with numbers of eosinophils within the epithelium. ZO-1 and E-cadherin expression were significantly lower in asthmatic than in nonasthmatic subjects. Expression of beta-catenin was not different. Our results suggest that the lower epithelial alpha-catenin, E-cadherin and (or) ZO-1 expression in patients with atopic asthma contributes to a defective airway epithelial barrier and a higher influx of eosinophils in the epithelium.Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the epithelium. Bronchial epithelial fragility has been reported in asthmatic patients, but little is known about the expression of TJ and AJ proteins in asthma. We studied epithelial expression of zonula occludens-1 (ZO-1) and AJ proteins E-cadherin, alpha-catenin, and beta-catenin in bronchial biopsies from nonatopic nonasthmatic (healthy) subjects (n = 14), and stable atopic asthmatic subjects (n = 22) at baseline conditions. Immunostaining for these proteins was semi-quantified for separate cellular compartments. E-cadherin, alpha-catenin and beta-catenin were present in the cellular membrane and less in the cytoplasm. Only beta-catenin was present in the nucleus in agreement with its potential function as transcription factor. ZO-1 was present in the apicolateral membrane of superficial cells. alpha-Catenin expression was significantly lower in subjects with asthma than without and correlated inversely with numbers of eosinophils within the epithelium. ZO-1 and E-cadherin expression were significantly lower in asthmatic than in nonasthmatic subjects. Expression of beta-catenin was not different. Our results suggest that the lower epithelial alpha-catenin, E-cadherin and (or) ZO-1 expression in patients with atopic asthma contributes to a defective airway epithelial barrier and a higher influx of eosinophils in the epithelium. Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the epithelium. Bronchial epithelial fragility has been reported in asthmatic patients, but little is known about the expression of TJ and AJ proteins in asthma. We studied epithelial expression of zonula occludens-1 (ZO-1) and AJ proteins E-cadherin, alpha-catenin, and beta-catenin in bronchial biopsies from nonatopic nonasthmatic (healthy) subjects (n = 14), and stable atopic asthmatic subjects (n = 22) at baseline conditions. Immunostaining for these proteins was semi-quantified for separate cellular compartments. E-cadherin, alpha-catenin and beta-catenin were present in the cellular membrane and less in the cytoplasm. Only beta-catenin was present in the nucleus in agreement with its potential function as transcription factor. ZO-1 was present in the apicolateral membrane of superficial cells. alpha-Catenin expression was significantly lower in subjects with asthma than without and correlated inversely with numbers of eosinophils within the epithelium. ZO-1 and E-cadherin expression were significantly lower in asthmatic than in nonasthmatic subjects. Expression of beta-catenin was not different. Our results suggest that the lower epithelial alpha-catenin, E-cadherin and (or) ZO-1 expression in patients with atopic asthma contributes to a defective airway epithelial barrier and a higher influx of eosinophils in the epithelium. Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the epithelium. Bronchial epithelial fragility has been reported in asthmatic patients, but little is known about the expression of TJ and AJ proteins in asthma. We studied epithelial expression of zonula occludens-1 (ZO-1) and AJ proteins E-cadherin, α-catenin, and β-catenin in bronchial biopsies from nonatopic nonasthmatic (healthy) subjects (n = 14), and stable atopic asthmatic subjects (n = 22) at baseline conditions. Immunostaining for these proteins was semi-quantified for separate cellular compartments. E-cadherin, α-catenin and β-catenin were present in the cellular membrane and less in the cytoplasm. Only β-catenin was present in the nucleus in agreement with its potential function as transcription factor. ZO-1 was present in the apicolateral membrane of superficial cells. α-Catenin expression was significantly lower in subjects with asthma than without and correlated inversely with numbers of eosinophils within the epithelium. ZO-1 and E-cadherin expression were significantly lower in asthmatic than in nonasthmatic subjects. Expression of β-catenin was not different. Our results suggest that the lower epithelial α-catenin, E-cadherin and (or) ZO-1 expression in patients with atopic asthma contributes to a defective airway epithelial barrier and a higher influx of eosinophils in the epithelium. Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may cause changes in epithelial morphology and integrity and potentially lead to faster trafficking of inflammatory cells through the epithelium. Bronchial epithelial fragility has been reported in asthmatic patients, but little is known about the expression of TJ and AJ proteins in asthma. We studied epithelial expression of zonula occludens-1 (ZO-1) and AJ proteins E-cadherin, α-catenin, and β-catenin in bronchial biopsies from nonatopic nonasthmatic (healthy) subjects (n = 14), and stable atopic asthmatic subjects (n = 22) at baseline conditions. Immunostaining for these proteins was semi-quantified for separate cellular compartments. E-cadherin, α-catenin and β-catenin were present in the cellular membrane and less in the cytoplasm. Only β-catenin was present in the nucleus in agreement with its potential function as transcription factor. ZO-1 was present in the apicolateral membrane of superficial cells. α-Catenin expression was significantly lower in subjects with asthma than without and correlated inversely with numbers of eosinophils within the epithelium. ZO-1 and E-cadherin expression were significantly lower in asthmatic than in nonasthmatic subjects. Expression of β-catenin was not different. Our results suggest that the lower epithelial α-catenin, E-cadherin and (or) ZO-1 expression in patients with atopic asthma contributes to a defective airway epithelial barrier and a higher influx of eosinophils in the epithelium. |
Abstract_FL | Les cellules épithéliales forment une barrière étanche contre les stimuli environnementaux grâce aux jonctions serrées (JS) et aux jonctions adhérentes (JA). Des défectuosités dans les protéines des JS et des JA pourraient entraîner des modifications dans l'intégrité et la morphologie épithéliales, et potentiellement accélérer la circulation des cellules inflammatoires à travers l'épithélium. La fragilité épithéliale bronchique chez des patients avec l'asthme est connue, mais on possède peu d'information sur l'expression des protéines des JS et des JA dans l'asthme. Nous avons examiné l'expression épithéliale de la zonula occludens-1 (ZO-1) et des protéines des JA, E-cadhérine, α-caténine et β-caténine, dans des biopsies bronchiques provenant de sujets sains non atopiques (n = 14) et de sujets asthmatiques atopiques stables (n = 22), en conditions basales. L'immunocoloration de ces protéines a été semi-quantifiée pour des compartiments cellulaires séparés. L'E-cadhérine, l' α-caténine et la β-caténine étaient présentes dans la membrane cellulaire et, dans un moindre degré, dans le cytoplasme. Seule la β-caténine était présente dans le noyau, en accord avec sa fonction potentielle de facteur de transcription. La ZO-1 était présente dans la membrane apico-latérale des cellules superficielles. L'expression de l' α-caténine a été significativement plus faible chez des patients avec l'asthme que chez les sujets sains, et a été inversement corrélée avec le taux d'éosinophiles dans l'épithélium. L'expression de la ZO-1 et celle de l'E-cadhérine ont été significativement plus faibles chez des patients avec l'asthme que chez les sujets sains. L'expression de la β-caténine a été identique. Nos résultats donnent à penser que la faible expression épithéliale de l' α-caténine, de l'E-cadhérine et (ou) de la ZO-1 chez des patients asthmatiques atopiques contribue à la présence d'une barrière épithéliale défectueuse dans les voies aériennes de même qu'à la présence d'un influx accru d'éosinophiles dans l'épithélium. |
Audience | Academic |
Author | Hoogsteden, H.C Baelemans, S.M.I de Boer, W.I Braunstahl, G.J Sharma, H.S Lambrecht, B.N |
Author_xml | – sequence: 1 givenname: W.I surname: de Boer fullname: de Boer, W.I email: deboer.pim@hetnet.nl organization: Department of Pulmonary Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands – sequence: 2 givenname: H.S surname: Sharma fullname: Sharma, H.S organization: Department of Surgical Oncology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands – sequence: 3 givenname: S.M.I surname: Baelemans fullname: Baelemans, S.M.I organization: Department of Pulmonary Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands – sequence: 4 givenname: H.C surname: Hoogsteden fullname: Hoogsteden, H.C organization: Department of Pulmonary Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands – sequence: 5 givenname: B.N surname: Lambrecht fullname: Lambrecht, B.N organization: Department of Pulmonary Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands – sequence: 6 givenname: G.J surname: Braunstahl fullname: Braunstahl, G.J organization: Department of Pulmonary Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands |
BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20276255$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/18418437$$D View this record in MEDLINE/PubMed https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-113380$$DView record from Swedish Publication Index |
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Keywords | Allergy Immunopathology Lung disease Respiratory disease Inflammation Epithelium Gene expression Adhesion Asthma Atopy Vertebrata Mammalia Bronchus disease Obstructive pulmonary disease Catenin |
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SubjectTerms | adhesion molecules adhésion molécules alpha Catenin - biosynthesis Asthma Asthma - metabolism Asthma - pathology asthme beta Catenin - biosynthesis Biological and medical sciences biopsie biopsy Bronchi - chemistry Bronchi - pathology Cadherins - biosynthesis catenins caténines Cell Adhesion Molecules - biosynthesis Cell junctions Eosinophils - chemistry Eosinophils - pathology Epithelial Attachment - chemistry Epithelial Attachment - pathology Epithelial Cells - chemistry Epithelial Cells - pathology epithelium Fundamental and applied biological sciences. Psychology Gene expression Genetic aspects Humans Immunohistochemistry Inflammation - metabolism Inflammation - pathology Inflammatory diseases Intercellular Junctions - chemistry Intercellular Junctions - pathology Junctional complexes (Epithelium) MEDICIN MEDICINE Membrane Proteins - biosynthesis Mucous Membrane - chemistry Mucous Membrane - pathology Phosphoproteins - biosynthesis Physiological aspects Proteins Vertebrates: anatomy and physiology, studies on body, several organs or systems Zonula Occludens-1 Protein épithélium |
Title | Altered expression of epithelial junctional proteins in atopic asthma: possible role in inflammation |
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