title: The effects of cigarette smoke condensate on vocal fold transepithelial resistance and inflammatory signaling in vocal fold fibroblasts.
abstract: OBJECTIVE
  In response to chronic cigarette smoke exposure, a subset of patients present with edematous vocal folds, characteristically referred to as Reinke's edema. This phenotype differs from the tissue changes associated with prolonged smoke exposure in the lower airway, and the mechanism underlying Reinke's edema remains poorly described. We hypothesize that the effects of smoke are diffuse and involve both the epithelium and mucosa.
  
  
  METHODS
  In vitro, ex vivo experiment.
  
  
  METHODS
  Transepithelial resistance (R(T) ) was quantified in an ex vivo, viable, porcine vocal fold model. Excised tissue was exposed to cigarette smoke condensate (CSC) and R(T) was computed at baseline and 1 and 4 hours after exposure. In vitro, human vocal fold fibroblasts were exposed to CSC. Cyclooxygenase 2 (COX-2), microsomal prostaglandin E synthase-1, and 15-hydroxyprostaglandin dehydrogenase mRNA expression were assessed at 4 hours. Prostaglandin E2 (PGE2) synthesis was quantified via immunoassay following 24 hours of CSC exposure.
  
  
  RESULTS
  CSC had no effect on R(T) . CSC did, however, induce COX-2 mRNA expression as well as its downstream lipid mediator PGE2. PGE2 metabolism appears to be regulated via both synthetic and degradative enzymes in response to cigarette smoke.
  
  
  CONCLUSIONS
  In vitro, CSC initiates an inflammatory response in vocal fold fibroblasts. However, in isolation, the epithelial resistance is not altered by CSC, at least acutely. These data may suggest a role for the interaction between the inflammatory response in the mucosa and compromised epithelial barrier function, as has been shown in other tissues.
authors.affiliation: Department of Otolaryngology, New York University School of Medicine, New York, New York 10016, USA. ryan.branski@nyumc.org
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Branski
authors.forename: Hang
authors.initials: H
authors.lastname: Zhou
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kraus
authors.forename: Mahalakshmi
authors.initials: M
authors.lastname: Sivasankar
mesh_terms: D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics; D066298:In Vitro Techniques; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D007819:Laryngeal Edema / Q000235:genetics / Q000503:physiopathology*; D007820:Laryngeal Mucosa / Q000503:physiopathology*; D007827:Laryngitis / Q000235:genetics / Q000503:physiopathology*; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D012907:Smoking / Q000009:adverse effects* / Q000503:physiopathology; D013638:Tars / Q000009:adverse effects*; D014827:Vocal Cords / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; D013638:Tars; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone