title: Prostaglandin (PG)E2 exhibits antifibrotic activity in vocal fold fibroblasts.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.affiliation: Department of Otolaryngology , New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Hang
authors.initials: H
authors.lastname: Zhou
authors.forename: Diane
authors.initials: D
authors.lastname: Felsen
authors.forename: Vlad C
authors.initials: VC
authors.lastname: Sandulache
authors.forename: Milan R
authors.initials: MR
authors.lastname: Amin
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kraus
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Branski
mesh_terms: D018929:Cell Culture Techniques; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D015232:Dinoprostone / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D014827:Vocal Cords / Q000166:cytology* / Q000187:drug effects; D014945:Wound Healing / Q000502:physiology*
chemical_list: D053773:Transforming Growth Factor beta1; D003094:Collagen; D015232:Dinoprostone