Relationship between time of exposure of laryngopharyngeal reflux and gene expression in laryngeal fibroblasts.
OBJECTIVE
Acid reflux is damaging to the laryngeal mucosa; however, the significance of the duration of reflux episodes has not been evaluated. The purpose of this study was to determine whether varying the exposure times at low pH with or without pepsin alters gene expression in laryngeal fibroblasts.


METHODS
Human false vocal fold and postcricoidal cultures were exposed to pH 4 or pH 5 media with and without pepsin for 10, 30, 60, and 240 seconds. Using a real-time polymerase chain reaction, we determined the messenger RNA expression of TGFbeta-1, VEGF, FGF-2, EGR-1, ATF-3, CTGF, MMP-1, MMP-2, and decorin.


RESULTS
Molecular responses were initiated at pH 5. Postcricoidal fibroblasts were more sensitive than false vocal fold fibroblasts to the presence of pepsin. Changes in transcript levels were dependent on acid exposure time, and the most significant changes were measured during the first 60 seconds after exposure.


CONCLUSIONS
Time of exposure to acid and pepsin needs to be taken into consideration when determining limit of pathology in pharyngeal reflux. Genes are identified that are induced by low pH and that may be of potential importance in the pathogenesis of reflux laryngitis.
Ylitalo
Riitta
R
Department of Otolaryngology-Head and Neck Surgery, Karolinska Institute, Stockholm, Sweden.
Thibeault
Susan L
SL
D002478:Cells, Cultured; D002648:Child; D005347:Fibroblasts / Q000378:metabolism*; D005764:Gastroesophageal Reflux / Q000378:metabolism / Q000503:physiopathology*; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007830:Larynx / Q000166:cytology*; D008297:Male; D010434:Pepsin A / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000187:drug effects*
D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D010434:Pepsin A