Altered matrix production in the distal airways of individuals with asthma.
(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:
https://lup.lub.lu.se/record/1665593
- author
- Nihlberg, Kristian LU ; Andersson Sjöland, Annika LU ; Tufvesson, Ellen LU ; Erjefält, Jonas LU ; Bjermer, Leif LU and Westergren-Thorsson, Gunilla LU
- organization
- publishing date
- 2010
- 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
- 2016-04-04 09:34:41
- date last changed
- 2022-01-29 18:32:34
@article{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<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.}},
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 = {{BMJ Publishing Group}},
series = {{Thorax}},
title = {{Altered matrix production in the distal airways of individuals with asthma.}},
url = {{http://dx.doi.org/10.1136/thx.2009.129320}},
doi = {{10.1136/thx.2009.129320}},
volume = {{65}},
year = {{2010}},
}