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Lung Fibroblast Proteoglycan Production Induced by Serum is Inhibited by Budesonide and Formoterol.

Todorova, Lizbet LU ; Gürcan, Eylem LU ; Miller-Larsson, Anna and Westergren-Thorsson, Gunilla LU (2006) In American Journal of Respiratory Cell and Molecular Biology 34(Sep 15). p.92-100
Abstract
Proteoglycans contribute to extracellular matrix remodeling in asthmatic airways. We investigated the effects of budesonide, a glucocorticoid, and formoterol, a long-acting beta(2)-adrenergic agonist, on serum-induced proteoglycan production by human lung fibroblasts. In 10% serum, total proteoglycan production was increased 1.5-fold (P < 0.01) compared with basal production in 0.4% serum. Budesonide (10(-8) M) reduced this increase by 44% (P < 0.01) and, whereas formoterol (10(-10)-10(-8) M) had no inhibitory effects, the drug combination abolished the increase (P < 0.01) without affecting fibroblast proliferation. This synergistic effect required functional glucocorticoid and beta-adrenergic receptors. The production of the... (More)
Proteoglycans contribute to extracellular matrix remodeling in asthmatic airways. We investigated the effects of budesonide, a glucocorticoid, and formoterol, a long-acting beta(2)-adrenergic agonist, on serum-induced proteoglycan production by human lung fibroblasts. In 10% serum, total proteoglycan production was increased 1.5-fold (P < 0.01) compared with basal production in 0.4% serum. Budesonide (10(-8) M) reduced this increase by 44% (P < 0.01) and, whereas formoterol (10(-10)-10(-8) M) had no inhibitory effects, the drug combination abolished the increase (P < 0.01) without affecting fibroblast proliferation. This synergistic effect required functional glucocorticoid and beta-adrenergic receptors. The production of the proteoglycans decorin, biglycan, perlecan, and versican was increased 2.5- to 5-fold (P < 0.01) in 10% serum. Combination treatment with budesonide (10(-8)M) and formoterol (10(-10) M) abolished this increase to a significantly greater extent than either drug alone. In 10% serum, only versican mRNA was increased 1.4-fold (P < 0.05), whereas decorin mRNA was reduced to 39% (P < 0.01) of basal expression. These serum effects were counteracted by the drug combination, but there were no significant differences between the combination and either drug alone. Thus, the budesonide and formoterol combination seems to synergistically control serum-induced proteoglycan production, primarily at the post-transcriptional level. In conclusion, the proteoglycan upregulation characteristic of asthmatic airways may be limited by combination therapy with budesonide and formoterol. (Less)
Please use this url to cite or link to this publication:
author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
airway remodeling, lung fibroblasts, beta(2)-agonists, glucocorticoids, proteoglycans
in
American Journal of Respiratory Cell and Molecular Biology
volume
34
issue
Sep 15
pages
92 - 100
publisher
American Thoracic Society
external identifiers
  • wos:000234390600011
  • pmid:16166747
  • scopus:29944435077
  • pmid:16166747
ISSN
1535-4989
DOI
10.1165/rcmb.2005-0048OC
language
English
LU publication?
yes
id
7b0465d5-7b95-44de-b67a-d71c7b0ffbd8 (old id 143628)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16166747&dopt=Abstract
date added to LUP
2016-04-01 11:54:45
date last changed
2021-04-13 01:18:03
@article{7b0465d5-7b95-44de-b67a-d71c7b0ffbd8,
  abstract     = {Proteoglycans contribute to extracellular matrix remodeling in asthmatic airways. We investigated the effects of budesonide, a glucocorticoid, and formoterol, a long-acting beta(2)-adrenergic agonist, on serum-induced proteoglycan production by human lung fibroblasts. In 10% serum, total proteoglycan production was increased 1.5-fold (P &lt; 0.01) compared with basal production in 0.4% serum. Budesonide (10(-8) M) reduced this increase by 44% (P &lt; 0.01) and, whereas formoterol (10(-10)-10(-8) M) had no inhibitory effects, the drug combination abolished the increase (P &lt; 0.01) without affecting fibroblast proliferation. This synergistic effect required functional glucocorticoid and beta-adrenergic receptors. The production of the proteoglycans decorin, biglycan, perlecan, and versican was increased 2.5- to 5-fold (P &lt; 0.01) in 10% serum. Combination treatment with budesonide (10(-8)M) and formoterol (10(-10) M) abolished this increase to a significantly greater extent than either drug alone. In 10% serum, only versican mRNA was increased 1.4-fold (P &lt; 0.05), whereas decorin mRNA was reduced to 39% (P &lt; 0.01) of basal expression. These serum effects were counteracted by the drug combination, but there were no significant differences between the combination and either drug alone. Thus, the budesonide and formoterol combination seems to synergistically control serum-induced proteoglycan production, primarily at the post-transcriptional level. In conclusion, the proteoglycan upregulation characteristic of asthmatic airways may be limited by combination therapy with budesonide and formoterol.},
  author       = {Todorova, Lizbet and Gürcan, Eylem and Miller-Larsson, Anna and Westergren-Thorsson, Gunilla},
  issn         = {1535-4989},
  language     = {eng},
  number       = {Sep 15},
  pages        = {92--100},
  publisher    = {American Thoracic Society},
  series       = {American Journal of Respiratory Cell and Molecular Biology},
  title        = {Lung Fibroblast Proteoglycan Production Induced by Serum is Inhibited by Budesonide and Formoterol.},
  url          = {http://dx.doi.org/10.1165/rcmb.2005-0048OC},
  doi          = {10.1165/rcmb.2005-0048OC},
  volume       = {34},
  year         = {2006},
}