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Prostaglandin (PG)E 2 exhibits antifibrotic activity in vocal fold fibroblasts
Author(s) -
Zhou Hang,
Felsen Diane,
Sandulache Vlad C.,
Amin Milan R.,
Kraus Dennis H.,
Branski Ryan C.
Publication year - 2011
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.21795
Subject(s) - prostaglandin e , secretion , prostaglandin e2 , transforming growth factor , endocrinology , medicine , prostaglandin , receptor , prostaglandin e2 receptor , agonist
Objectives/Hypothesis. Prostaglandin (PG)E 2 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 PGE 2 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, PGE 2 , and specific EP receptor agonists. Basal HVFF migratory rate was also quantified in response to PGE 2 . TGF‐β1 induced COX‐2 mRNA expression/PGE 2 secretion was assayed. Excised vocal folds were subjected to exogenous IL‐1β; PGE 2 secretion into the supernatant was then assayed. Results: TGF‐β1‐induced collagen secretion was blunted in a dose‐dependent manner in response to PGE 2 . This effect appears to be mediated primarily through the EP1 and EP2 receptors. TGF‐β1 induced COX‐2 mRNA expression and PGE 2 secretion. In our organ culture model, IL‐1β stimulated PGE 2 secretion in a dose‐dependent manner. Conclusions: PGE 2 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 PGE 2 signaling, specifically. In addition, our organ culture model may prove useful as a means to quantify biological phenomena in the vocal folds.