Abstract
Background: The balance between production and degradation of extracellular matrix is crucial in maintaining normal tissue structure. Budesonide is known to have anti-inflammatory effects, but its effect on fibroblast-mediated tissue repair and remodeling has not been fully studied.
Methods: Using human fetal lung fibroblasts (HFL-1 cells) in a three-dimensional collagen gel culture system, the current study investigated the effect of budesonide (1-1000 nM) on collagen gel contraction and degradation in the presence or absence of inflammatory cytokines (IL-1β and TNF-α; 5 ng/ml each) and, in order to activate latent proteases, the serine protease trypsin (0.25 μg/ml).
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 metalloproteinases (MMP) -1, -3 and -9 induced by the cytokines (p<0.05). Exposure to the cytokines plus trypsin increased collagen degradation and activation of the MMPs. Budesonide blocked both the enhanced collagen degradation (p<0.01) and suppressed the trypsin-mediated activation of cytokine-induced MMP-9 and MMP-3. Similar effects were observed with dexamethasone (1 μM), suggesting a class effect.
Conclusions: These findings suggest that budesonide directly modulates contraction of collagen and can decrease collagen degradation under inflammatory conditions through suppressing release and activation of MMPs. By modulating the release and activity of MMPs, inhaled budesonide may be able to modify airway tissue repair and remodeling.
- © 2011 ERS