Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma

Rationale: Convincing evidence of epithelial damage and aberrant repair exists in adult asthmatic airways, even in the absence of inflammation. However, comparable studies in children have been limited by access and availability of clinical samples. Objectives: To determine whether bronchial epithel...

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Main Authors: Kicic, Anthony, Sutanto, E.N., Stevens, P.T., Knight, D.A., Stick, S.M.
Format: Journal Article
Language:English
Published: AMER THORACIC SOC 2006
Subjects:
Online Access:http://hdl.handle.net/20.500.11937/76824
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author Kicic, Anthony
Sutanto, E.N.
Stevens, P.T.
Knight, D.A.
Stick, S.M.
author_facet Kicic, Anthony
Sutanto, E.N.
Stevens, P.T.
Knight, D.A.
Stick, S.M.
author_sort Kicic, Anthony
building Curtin Institutional Repository
collection Online Access
description Rationale: Convincing evidence of epithelial damage and aberrant repair exists in adult asthmatic airways, even in the absence of inflammation. However, comparable studies in children have been limited by access and availability of clinical samples. Objectives: To determine whether bronchial epithelial cells from children with asthma are inherently distinct from those obtained from children without asthma. Methods: Epithelial cells were obtained by nonbronchoscopic bronchial brushing of children with mild asthma (n = 7), atopic children without asthma (n = 9), and healthy children (n = 12). Cells were subject to morphologic, biochemical, molecular, and functional assessment. Responses were also compared with commercially available epithelial cultures and the transformed cell line 16HBE140. Results: All epithelial cells exhibited a "cobblestone" morphology, which was maintained throughout culture and repeated passage. Expression of cytokeratin 19 varied, with disease phenotype being greatest in healthy nonatopics and lowest in asthmatics. In contrast, expression of cytokeratin 5/14 was greatest in asthmatic samples and least in healthy nonatopic samples. Asthmatic epithelial cells also spontaneously produced significantly greater amounts of interleukin (IL)-6, prostaglandin E2, and epidermal growth factor, and equivalent amounts of IL-1β and soluble intracellular adhesion molecule-1, but significantly lower amounts of transforming growth factor β1. This profile was maintained through successive passages. Asthmatic epithelial cells also exhibited greater rates of proliferation than nonasthmatic cells. Conclusions: This study has shown that epithelial cells from children with mild asthma are intrinsically different both biochemically and functionally compared with epithelial cells from children without asthma. Importantly, these differences are maintained over successive passages, suggesting that they are not dependent on an in vivo environment.
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spelling curtin-20.500.11937-768242019-11-12T08:17:17Z Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma Kicic, Anthony Sutanto, E.N. Stevens, P.T. Knight, D.A. Stick, S.M. Science & Technology Life Sciences & Biomedicine Critical Care Medicine Respiratory System General & Internal Medicine airway asthma bronchial epithelium cell nonbronchoscopic brushing TRANSFORMING GROWTH-FACTOR COLONY-STIMULATING FACTOR NECROSIS-FACTOR-ALPHA AIRWAY EPITHELIUM MILD ASTHMA BASAL-CELLS EXPRESSION PROLIFERATION INTERLEUKIN-8 CULTURE Rationale: Convincing evidence of epithelial damage and aberrant repair exists in adult asthmatic airways, even in the absence of inflammation. However, comparable studies in children have been limited by access and availability of clinical samples. Objectives: To determine whether bronchial epithelial cells from children with asthma are inherently distinct from those obtained from children without asthma. Methods: Epithelial cells were obtained by nonbronchoscopic bronchial brushing of children with mild asthma (n = 7), atopic children without asthma (n = 9), and healthy children (n = 12). Cells were subject to morphologic, biochemical, molecular, and functional assessment. Responses were also compared with commercially available epithelial cultures and the transformed cell line 16HBE140. Results: All epithelial cells exhibited a "cobblestone" morphology, which was maintained throughout culture and repeated passage. Expression of cytokeratin 19 varied, with disease phenotype being greatest in healthy nonatopics and lowest in asthmatics. In contrast, expression of cytokeratin 5/14 was greatest in asthmatic samples and least in healthy nonatopic samples. Asthmatic epithelial cells also spontaneously produced significantly greater amounts of interleukin (IL)-6, prostaglandin E2, and epidermal growth factor, and equivalent amounts of IL-1β and soluble intracellular adhesion molecule-1, but significantly lower amounts of transforming growth factor β1. This profile was maintained through successive passages. Asthmatic epithelial cells also exhibited greater rates of proliferation than nonasthmatic cells. Conclusions: This study has shown that epithelial cells from children with mild asthma are intrinsically different both biochemically and functionally compared with epithelial cells from children without asthma. Importantly, these differences are maintained over successive passages, suggesting that they are not dependent on an in vivo environment. 2006 Journal Article http://hdl.handle.net/20.500.11937/76824 10.1164/rccm.200603-392OC English AMER THORACIC SOC restricted
spellingShingle Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
airway
asthma
bronchial epithelium
cell
nonbronchoscopic brushing
TRANSFORMING GROWTH-FACTOR
COLONY-STIMULATING FACTOR
NECROSIS-FACTOR-ALPHA
AIRWAY EPITHELIUM
MILD ASTHMA
BASAL-CELLS
EXPRESSION
PROLIFERATION
INTERLEUKIN-8
CULTURE
Kicic, Anthony
Sutanto, E.N.
Stevens, P.T.
Knight, D.A.
Stick, S.M.
Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma
title Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma
title_full Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma
title_fullStr Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma
title_full_unstemmed Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma
title_short Intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma
title_sort intrinsic biochemical and functional differences in bronchial epithelial cells of children with asthma
topic Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
Respiratory System
General & Internal Medicine
airway
asthma
bronchial epithelium
cell
nonbronchoscopic brushing
TRANSFORMING GROWTH-FACTOR
COLONY-STIMULATING FACTOR
NECROSIS-FACTOR-ALPHA
AIRWAY EPITHELIUM
MILD ASTHMA
BASAL-CELLS
EXPRESSION
PROLIFERATION
INTERLEUKIN-8
CULTURE
url http://hdl.handle.net/20.500.11937/76824