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:
https://lup.lub.lu.se/record/1644861
- author
- Todorova, Lizbet
LU
; Bjermer, Leif
; Miller-Larsson, Anna
and Westergren-Thorsson, Gunilla
LU
- organization
- publishing date
- 2010
- 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
- 2016-04-01 10:30:26
- date last changed
- 2024-02-05 06:54:12
@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 </= 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.}},
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 = {{https://lup.lub.lu.se/search/files/1903756/1685556.pdf}},
doi = {{10.1016/j.rmed.2010.06.015}},
volume = {{104}},
year = {{2010}},
}