Prostaglandin (PG)E2 exhibits antifibrotic activity in vocal fold fibroblasts.
2011
Objectives/Hypothesis.
Prostaglandin (PG)E2 has been implicated in a variety of disease processes. It has been described as antifibrotic in the lower airway, yet scar-inducing in the skin. We seek to describe the effects of PGE2 on vocal fold fibroblasts and its interactions with transforming growth factor (TGF)-β1. In addition, we describe a novel organotypic model, a critical step in the development of therapeutic trials.
Study Design.
In vitro, ex vivo.
Methods:
Collagen secretion by human vocal fold fibroblasts (HVFF) was assayed in response to TGF-β1, PGE2, and specific EP receptor agonists. Basal HVFF migratory rate was also quantified in response to PGE2. TGF-β1 induced COX-2 mRNA expression/PGE2 secretion was assayed. Excised vocal folds were subjected to exogenous IL-1β; PGE2 secretion into the supernatant was then assayed.
Results:
TGF-β1-induced collagen secretion was blunted in a dose-dependent manner in response to PGE2. This effect appears to be mediated primarily through the EP1 and EP2 receptors. TGF-β1 induced COX-2 mRNA expression and PGE2 secretion. In our organ culture model, IL-1β stimulated PGE2 secretion in a dose-dependent manner.
Conclusions:
PGE2 is antifibrotic; this finding suggests that the upper airway response to this inflammatory mediator differs significantly from the lower airway. These data have important clinical implications for a variety of pathological processes. Furthermore, exogenous TGF-β1 elicits induction of COX-2, suggesting inherent complexity regarding these processes and PGE2 signaling, specifically. In addition, our organ culture model may prove useful as a means to quantify biological phenomena in the vocal folds.
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