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 inCanadian journal of physiology and pharmacology Vol. 86; no. 3; pp. 105 - 112
Main Authors de Boer, W.I, Sharma, H.S, Baelemans, S.M.I, Hoogsteden, H.C, Lambrecht, B.N, Braunstahl, G.J
Format Journal Article
LanguageEnglish
Published Ottawa, ON National Research Council of Canada 01.03.2008
NRC Research Press
Canadian Science Publishing NRC Research Press
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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.
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
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  surname: de Boer
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  givenname: H.S
  surname: Sharma
  fullname: Sharma, H.S
  organization: Department of Surgical Oncology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
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  givenname: S.M.I
  surname: Baelemans
  fullname: Baelemans, S.M.I
  organization: Department of Pulmonary Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
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  givenname: H.C
  surname: Hoogsteden
  fullname: Hoogsteden, H.C
  organization: Department of Pulmonary Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
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  surname: Braunstahl
  fullname: Braunstahl, G.J
  organization: Department of Pulmonary Medicine, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
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Issue 3
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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Snippet Epithelial cells form a tight barrier against environmental stimuli via tight junctions (TJs) and adherence junctions (AJs). Defects in TJ and AJ proteins may...
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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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