Cyclooxygenase-2 signaling in vocal fold fibroblasts Journal Article

Authors: Branski, R. C.; Zhou, H.; Sandulache, V. C.; Chen, J.; Felsen, D.; Kraus, D. H.
Article Title: Cyclooxygenase-2 signaling in vocal fold fibroblasts
Abstract: Objectives/Hypothesis: Inflammation and its role in a coordinated fibroplastic response, which disrupts the structure of the vocal folds following injury, is critical. Cyclooxygenase-2 (COX-2) is an important enzyme involved in both inflammation and fibrosis; in addition, it is a prime target for therapeutic intervention. We sought to study this pathway in vocal fold fibroblasts to provide a foundation for future interventional studies. Study Design: In vitro. Methods: Human vocal fold fibroblasts were incubated with IL-1β to determine the effects on COX-2 signaling, along with upstream regulatory mechanisms and downstream mediators of wound healing. In vitro methods to assess mRNA expression, as well as intracellular and secreted protein (sodium dodecyl sulfate polyacrylamide gel electrophoresis and enzyme-linked immunosorbent assay) were employed. Results: IL-1β regulation of COX-2 mRNA and protein levels was dose and time dependent and IL-1β altered PGE 2 metabolism, via regulation of both synthetic and degradative enzymes. IL-1β increased nuclear factor (NF)-κB activation and nuclear translocation. Inhibition of the p50 and p65 subunits of NF-κB decreased IL-1β-induced COX-2 transcription. IL-1β also altered mRNA expression of four cell-surface prostaglandin receptors. Conclusions: Inflammation and fibrosis are important in the vocal fold pathophysiologic response to injury. Our data suggest that COX-2 and PGE2 are inducible in human vocal fold fibroblasts, and this response appears to be NF-κB-dependent. We purport this fundamental investigation will lead to increased insight regarding injury and repair in the vocal folds, with the ultimate goal of developing novel clinical care paradigms. © 2010 The American Laryngological, Rhinological and Otological Society, Inc.
Keywords: signal transduction; controlled study; protein expression; unclassified drug; gene translocation; human cell; vocal cord; cells, cultured; steady state; interleukin 1beta; inflammation; immunoglobulin enhancer binding protein; genetic transcription; transcription, genetic; wound healing; gene expression regulation; regulatory mechanism; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; cyclooxygenase 2; prostaglandin; prostaglandin e2; nf-kappa b; western blotting; vocal fold; fibroblast; fibroblasts; vocal cords; active transport, cell nucleus; enzyme-linked immunosorbent assay; polyacrylamide gel electrophoresis; cyclooxygenase; nf-κb; immunoglobulin enhancer binding protein p50; immunoglobulin enhancer binding protein p65; dose time effect relation; prostaglandin synthesis; dinoprostone; interleukin-1beta; receptors, prostaglandin
Journal Title: Laryngoscope
Volume: 120
Issue: 9
ISSN: 0023-852X
Publisher: Wiley Blackwell  
Date Published: 2010-09-01
Start Page: 1826
End Page: 1831
Language: English
DOI: 10.1002/lary.21017
PUBMED: 20717945
PROVIDER: scopus
PMCID: PMC3132797
Notes: --- - "Export Date: 20 April 2011" - "CODEN: LARYA" - "Source: Scopus"
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MSK Authors
  1. Dennis Kraus
    259 Kraus
  2. Ryan C Branski
    22 Branski
  3. Hang Zhou
    1 Zhou