title: Prostaglandin E2 is activated by airway injury and regulates fibroblast cytoskeletal dynamics.
abstract: OBJECTIVE
  To characterize the activation of cyclooxygenase (COX)-2/prostaglandin (PG) E2 signaling during airway mucosal repair and its subsequent role during the wound healing process.
  
  
  METHODS
  Prospective animal study.
  
  
  METHODS
  The subglottis was approached via cricothyroidotomy. Sham airways were closed, and wounded airways were subjected to laser injury and closed. Subglottic tissue was harvested at 12 hours, 24 hours, 48 hours, and 72 hours postinjury. Secretions were collected preoperatively and at time of sacrifice. Inflammatory gene expression was analyzed using quantitative reverse transcriptase polymerase chain reaction. Subglottic/tracheal explants were exposed to exogenous IL-1beta in the presence or absence of COX inhibitors. Explant-produced PGE2 levels were assayed using enzyme linked immunoassays. Human airway fibroblast migration and collagen contraction were assayed in the presence or absence of prostaglandin E2.
  
  
  RESULTS
  Laser injury triggers a rapid, dose-dependent increase in mucosal IL-1beta and COX-2 gene expression, with an anatomical distribution proportional to the distance from the site of injury. Gene upregulation correlates with dose-dependent increases in PGE2 mucosal secretion levels. Ex vivo analysis indicates IL-1beta is responsible for the activation of the COX-2 / PGE2 pathway. Prostaglandin E2 differentially inhibits airway fibroblast migration and contraction in a specific, dose-dependent manner.
  
  
  CONCLUSIONS
  PGE2 is activated during mucosal inflammation and acts to decrease fibroplastic activity in the mucosal wound bed. During subglottic stenosis (SGS) development, the levels of PGE2 generated in response to injury may be insufficient to blunt the intrinsically fibroplastic phenotype of SGS fibroblasts, resulting in excessive scarring.
authors.affiliation: Division of Pediatric Otolaryngology, Children's Hospital of Pittsburgh, Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15201, USA.
authors.forename: Vlad C
authors.initials: VC
authors.lastname: Sandulache
authors.forename: Tripti
authors.initials: T
authors.lastname: Singh
authors.forename: Ha Sheng
authors.initials: HS
authors.lastname: Li-Korotky
authors.forename: Chia Y
authors.initials: CY
authors.lastname: Lo
authors.forename: Todd D
authors.initials: TD
authors.lastname: Otteson
authors.forename: Mark
authors.initials: M
authors.lastname: Barsic
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Dohar
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Hebda
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000502:physiology*; D007375:Interleukin-1 / Q000494:pharmacology; D007834:Lasers; D011446:Prospective Studies; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014132:Trachea / Q000293:injuries*; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D051546:Cyclooxygenase 2; D015232:Dinoprostone