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)-ฮฒ1. 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-ฮฒ1, pge2 , and specific ep receptor agonists. basal hvff migratory rate was also quantified in response to pge2 . tgf-ฮฒ1 induced cox-2 mrna expression/pge2 secretion was assayed. excised vocal folds were subjected to exogenous il-1ฮฒ; pge2 secretion into the supernatant was then assayed.
Results:
Tgf-ฮฒ1-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-ฮฒ1 induced cox-2 mrna expression and pge2 secretion. in our organ culture model, il-1ฮฒ 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-ฮฒ1 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.