-
Journal of Inflammation Research
- About Dovepress
Open access peer-reviewed scientific and medical journals.
- Open Access
Dove Medical Press is now a member of the Open Access Initiative
- An Author's Guide
A guide to help authors get their paper published.
- Advocacy
Support Open Access and Dove Press
- Reprints
Promotional Article Monitoring - further details
- Favored Author Program
Real benefits for authors, including fast-track processing of papers.
Effect of budesonide on fibroblast-mediated collagen gel contraction and degradation
Original Research
(2049) Total Article Views
Authors: Fang Q, Schulte NA, Kim H, Kobayashi T, Wang X, Miller-Larsson A, Wieslander E, Toews ML, Liu X, Rennard SI
Published Date February 2013 Volume 2013:6 Pages 25 - 33
DOI: http://dx.doi.org/10.2147/JIR.S35136
Received: | 19 June 2012 |
---|---|
Accepted: | 09 August 2012 |
Published: | 27 February 2013 |
1Pulmonary and Critical Care Department, Beijing Shijitan Hospital, Capital Medical University, Beijing, People's Republic of China; 2Pulmonary, Critical Care, Sleep and Allergy Division, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; 3Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA; 4Pulmonary and Critical Care Division, WonKwang University, Kunpo Medical Center, Seoul, Republic of Korea; 5Mie University Graduate School of Medicine, Tsu City, Japan; 6AstraZeneca R&D Molndal, Molndal, Sweden
Background: The balance between production and degradation of extracellular matrix is crucial in maintaining normal tissue structure. This study was designed to investigate the effect of budesonide on fibroblast-mediated tissue repair and remodeling.
Methods: Using human fetal lung fibroblasts in a three-dimensional collagen gel culture system, we investigated the effect of budesonide (1–1000 nM) on collagen gel contraction and degradation in the presence or absence of inflammatory cytokines (interleukin-1β and tumor necrosis factor α; 5 ng/mL each) and, in order to activate latent proteases, serine protease trypsin 0.25 µg/mL. The effects of budesonide on metalloproteinase production and activation were also investigated.
Results: Inflammatory cytokines significantly inhibited collagen gel contraction mediated by lung fibroblasts. Budesonide counteracted the effect of cytokines in a concentration-dependent manner (to 50%, P < 0.01). Budesonide 100 nM almost completely inhibited the release and mRNA expression of metalloproteinase-1, metalloproteinase-3, and metalloproteinase-9 induced by the cytokines (P < 0.05). Exposure to the cytokines plus trypsin increased collagen degradation and conversion of the metalloproteinases to lower molecular weight forms corresponding to their active forms. Budesonide blocked both enhanced collagen degradation (P < 0.01) and suppressed trypsin-mediated conversion of cytokine-induced metalloproteinase-9 and metalloproteinase-3 to lower molecular weight forms. Similar effects were observed with dexamethasone 1 µM, suggesting a class effect.
Conclusion: These findings demonstrate that budesonide directly modulates contraction of collagen gels and can decrease collagen degradation under inflammatory conditions. The mechanism of this effect is through suppressing gene expression, release, and activation of metalloproteinases. By modulating the release and activity of metalloproteinases, inhaled budesonide may be able to modify airway tissue repair and remodeling.
Keywords: metalloproteinase, budesonide, tissue remodeling
Post to:
Cannotea Citeulike Del.icio.us Facebook LinkedIn Twitter
Other articles by Dr Stephen Rennard
Readers of this article also read:
- Testimonials
"You do a tremendous job!!" Ruben Restrepo, University of Texas Health Science Center, San Antonio.
- Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite
- Inflammatory mechanisms in the lung
- Inflammatory mediators: Parallels between cancer biology and stem cell therapy
- Effects of 4:1 carbohydrate/protein solution versus a carbohydrate-alone solution on IL-6, TNF-α, and cortisol during prolonged cycling in hot environmental conditions