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.
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.
Authors: F W Frantz; D A Bettinger; J H Haynes; D E Johnson; K M Harvey; H P Dalton; D R Yager; R F Diegelmann; I K Cohen Journal: J Pediatr Surg Date: 1993-03 Impact factor: 2.545
Authors: Vlad C Sandulache; Tripti Singh; Ha Sheng Li-Korotky; Chia Y Lo; Todd D Otteson; Mark Barsic; Joseph E Dohar; Patricia A Hebda Journal: Laryngoscope Date: 2009-07 Impact factor: 3.325
Authors: Ryan C Branski; Silvia S Barbieri; Babette B Weksler; Benjamin Saltman; Priya Krishna; Dennis H Kraus; Nalini V Broadbelt; Jie Chen; Dix P Poppas; Diane Felsen Journal: Ann Otol Rhinol Laryngol Date: 2009-03 Impact factor: 1.547