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Altered matrix production in the distal airways of individuals with asthma.

Nihlberg, Kristian LU ; Andersson Sjöland, Annika LU ; Tufvesson, Ellen LU ; Erjefält, Jonas LU ; Bjermer, Leif LU and Westergren-Thorsson, Gunilla LU (2010) In Thorax 65(8). p.670-676
Abstract
BACKGROUND AND AIMS: Although increasing evidence suggests involvement of the distal airway in all stages of asthma, it is not known whether structural changes (defined as airway remodelling) occur in the distal airways of subjects with mild asthma and those with atopy. The aim of this study was to compare control subjects and those with mild asthma in relation to fibroblast phenotypes and remodelling in central and distal airways. METHODS: Distal and central fibroblasts from controls (n=12) and patients with mild asthma (n=11) were cultured and incubated for 24 h with 0.4% serum, or stimulated with transforming growth factor beta1 (TGFbeta1). [(35)S]Sulfate-labelled proteoglycans in culture medium were analysed by ion exchange... (More)
BACKGROUND AND AIMS: Although increasing evidence suggests involvement of the distal airway in all stages of asthma, it is not known whether structural changes (defined as airway remodelling) occur in the distal airways of subjects with mild asthma and those with atopy. The aim of this study was to compare control subjects and those with mild asthma in relation to fibroblast phenotypes and remodelling in central and distal airways. METHODS: Distal and central fibroblasts from controls (n=12) and patients with mild asthma (n=11) were cultured and incubated for 24 h with 0.4% serum, or stimulated with transforming growth factor beta1 (TGFbeta1). [(35)S]Sulfate-labelled proteoglycans in culture medium were analysed by ion exchange chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Proliferation was measured with crystal violet, and exhaled nitric oxide was measured by the fractional nitric oxide technique. RESULTS: Vesican production from distal fibroblasts was significantly elevated in patients with asthma compared with controls (p<0.001), and the percentage collagen-positive area in distal asthma tissue was also enhanced compared with controls (p<0.01). In addition, distal asthma fibroblasts had reduced proliferation capacity compared with those of controls (by 24%; p<0.01). Furthermore, the alveolar nitric oxide concentration was correlated to distal biglycan and perlecan production of subjects with asthma (r=-0.857, p<0.05 and r=-0.750, p<0.05 respectively) CONCLUSION: It is shown that centrally and distally derived fibroblasts differ in their proteoglycan production and proliferation between central and distal tissue, and in those with asthma compared with controls. It is also demonstrated that remodelling is present in distal lung of subjects with mild asthma. This may be of importance in airway remodelling and asthma progression. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Thorax
volume
65
issue
8
pages
670 - 676
publisher
BMJ Publishing Group
external identifiers
  • WOS:000280527600004
  • PMID:20685740
  • Scopus:77956020972
ISSN
1468-3296
DOI
10.1136/thx.2009.129320
language
English
LU publication?
yes
id
6222c6eb-f8a0-44b9-bd19-8dab4f8caabc (old id 1665593)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20685740?dopt=Abstract
date added to LUP
2010-09-03 08:43:50
date last changed
2016-10-13 04:33:11
@misc{6222c6eb-f8a0-44b9-bd19-8dab4f8caabc,
  abstract     = {BACKGROUND AND AIMS: Although increasing evidence suggests involvement of the distal airway in all stages of asthma, it is not known whether structural changes (defined as airway remodelling) occur in the distal airways of subjects with mild asthma and those with atopy. The aim of this study was to compare control subjects and those with mild asthma in relation to fibroblast phenotypes and remodelling in central and distal airways. METHODS: Distal and central fibroblasts from controls (n=12) and patients with mild asthma (n=11) were cultured and incubated for 24 h with 0.4% serum, or stimulated with transforming growth factor beta1 (TGFbeta1). [(35)S]Sulfate-labelled proteoglycans in culture medium were analysed by ion exchange chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Proliferation was measured with crystal violet, and exhaled nitric oxide was measured by the fractional nitric oxide technique. RESULTS: Vesican production from distal fibroblasts was significantly elevated in patients with asthma compared with controls (p&lt;0.001), and the percentage collagen-positive area in distal asthma tissue was also enhanced compared with controls (p&lt;0.01). In addition, distal asthma fibroblasts had reduced proliferation capacity compared with those of controls (by 24%; p&lt;0.01). Furthermore, the alveolar nitric oxide concentration was correlated to distal biglycan and perlecan production of subjects with asthma (r=-0.857, p&lt;0.05 and r=-0.750, p&lt;0.05 respectively) CONCLUSION: It is shown that centrally and distally derived fibroblasts differ in their proteoglycan production and proliferation between central and distal tissue, and in those with asthma compared with controls. It is also demonstrated that remodelling is present in distal lung of subjects with mild asthma. This may be of importance in airway remodelling and asthma progression.},
  author       = {Nihlberg, Kristian and Andersson Sjöland, Annika and Tufvesson, Ellen and Erjefält, Jonas and Bjermer, Leif and Westergren-Thorsson, Gunilla},
  issn         = {1468-3296},
  language     = {eng},
  number       = {8},
  pages        = {670--676},
  publisher    = {ARRAY(0x876f300)},
  series       = {Thorax},
  title        = {Altered matrix production in the distal airways of individuals with asthma.},
  url          = {http://dx.doi.org/10.1136/thx.2009.129320},
  volume       = {65},
  year         = {2010},
}