Advanced

Relationship between matrix production by bronchial fibroblasts and lung function and AHR in asthma.

Todorova, Lizbet LU ; Bjermer, Leif; Miller-Larsson, Anna and Westergren-Thorsson, Gunilla LU (2010) In Respiratory Medicine 104(12). p.1799-1808
Abstract
The reasons for enhanced deposition of extracellular matrix in the airways of asthmatic patients and the subsequent consequences on lung function are uncertain. Here, we investigated the synthesis of procollagen I and proteoglycans, the activity of various metalloproteinases (MMPs) and the production of their inhibitor TIMP-1 in biopsy-derived bronchial fibroblasts from eight patients with stable mild-to-moderate asthma, and how they are related to patients' lung function and airway hyperreactivity (AHR). Following 24-h fibroblast incubation in 0.4% serum, procollagen I carboxyterminal propeptide (PICP), TIMP-1 and MMP-1 in cell media were analysed by ELISA, MMP-2, MMP-3, MMP-9 by zymography and total proteoglycan production by... (More)
The reasons for enhanced deposition of extracellular matrix in the airways of asthmatic patients and the subsequent consequences on lung function are uncertain. Here, we investigated the synthesis of procollagen I and proteoglycans, the activity of various metalloproteinases (MMPs) and the production of their inhibitor TIMP-1 in biopsy-derived bronchial fibroblasts from eight patients with stable mild-to-moderate asthma, and how they are related to patients' lung function and airway hyperreactivity (AHR). Following 24-h fibroblast incubation in 0.4% serum, procollagen I carboxyterminal propeptide (PICP), TIMP-1 and MMP-1 in cell media were analysed by ELISA, MMP-2, MMP-3, MMP-9 by zymography and total proteoglycan production by [(35)S]-sulphate-incorporation/ion chromatography. Patients' FEV(1)% predicted and methacholine log PD(20) negatively correlated with PICP synthesized by patients' bronchial fibroblasts (r = -0.74 and r = -0.71, respectively). PICP and proteoglycan amounts positively correlated (0.8 </= r </= 0.9) with MMP-2 and MMP-3 activity. A positive correlation (r = 0.75) was also found between proteoglycan production and TIMP-1. There was no correlation between MMP-9 activity and PICP or proteoglycan production. MMP-9 activity positively correlated with patients' FEV(1)% predicted (r = 0.97) and methacholine log PD(20) (r = 0.86), whereas negative associations (-0.6 </= r </= -0.7) were observed for MMP-2 and MMP-3. In stable mild-to-moderate asthma, increased procollagen I synthesis and activity of MMP-2 and MMP-3 in bronchial fibroblasts may negatively affect patients' lung function and AHR. In contrast, MMP-9 activity was not associated with procollagen or proteoglycan production, or worsening of patients' lung function and AHR. An enhanced production of procollagen I and proteoglycans might be a result of a negative feedback from their degradation by MMP-2 and MMP-3. (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
Respiratory Medicine
volume
104
issue
12
pages
1799 - 1808
publisher
Elsevier
external identifiers
  • wos:000284812900009
  • pmid:20637583
  • scopus:78650001101
ISSN
1532-3064
DOI
10.1016/j.rmed.2010.06.015
language
English
LU publication?
yes
id
3d9a6580-828b-42a4-ba0e-11eb61ec86b9 (old id 1644861)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20637583?dopt=Abstract
date added to LUP
2010-08-05 09:43:42
date last changed
2018-05-29 10:57:01
@article{3d9a6580-828b-42a4-ba0e-11eb61ec86b9,
  abstract     = {The reasons for enhanced deposition of extracellular matrix in the airways of asthmatic patients and the subsequent consequences on lung function are uncertain. Here, we investigated the synthesis of procollagen I and proteoglycans, the activity of various metalloproteinases (MMPs) and the production of their inhibitor TIMP-1 in biopsy-derived bronchial fibroblasts from eight patients with stable mild-to-moderate asthma, and how they are related to patients' lung function and airway hyperreactivity (AHR). Following 24-h fibroblast incubation in 0.4% serum, procollagen I carboxyterminal propeptide (PICP), TIMP-1 and MMP-1 in cell media were analysed by ELISA, MMP-2, MMP-3, MMP-9 by zymography and total proteoglycan production by [(35)S]-sulphate-incorporation/ion chromatography. Patients' FEV(1)% predicted and methacholine log PD(20) negatively correlated with PICP synthesized by patients' bronchial fibroblasts (r = -0.74 and r = -0.71, respectively). PICP and proteoglycan amounts positively correlated (0.8 &lt;/= r &lt;/= 0.9) with MMP-2 and MMP-3 activity. A positive correlation (r = 0.75) was also found between proteoglycan production and TIMP-1. There was no correlation between MMP-9 activity and PICP or proteoglycan production. MMP-9 activity positively correlated with patients' FEV(1)% predicted (r = 0.97) and methacholine log PD(20) (r = 0.86), whereas negative associations (-0.6 &lt;/= r &lt;/= -0.7) were observed for MMP-2 and MMP-3. In stable mild-to-moderate asthma, increased procollagen I synthesis and activity of MMP-2 and MMP-3 in bronchial fibroblasts may negatively affect patients' lung function and AHR. In contrast, MMP-9 activity was not associated with procollagen or proteoglycan production, or worsening of patients' lung function and AHR. An enhanced production of procollagen I and proteoglycans might be a result of a negative feedback from their degradation by MMP-2 and MMP-3.},
  author       = {Todorova, Lizbet and Bjermer, Leif and Miller-Larsson, Anna and Westergren-Thorsson, Gunilla},
  issn         = {1532-3064},
  language     = {eng},
  number       = {12},
  pages        = {1799--1808},
  publisher    = {Elsevier},
  series       = {Respiratory Medicine},
  title        = {Relationship between matrix production by bronchial fibroblasts and lung function and AHR in asthma.},
  url          = {http://dx.doi.org/10.1016/j.rmed.2010.06.015},
  volume       = {104},
  year         = {2010},
}