Rapamycin inhibits human laryngotracheal stenosis-derived fibroblast proliferation, metabolism, and function in vitro

Daryan R. Namba, Garret Ma, Idris Samad, Dacheng Ding, Vinciya Pandian, Jonathan D. Powell, Maureen R. Horton, Alexander T. Hillel

Research output: Contribution to journalArticle

Abstract

Objective. To determine if rapamycin inhibits the growth, function, and metabolism of human laryngotracheal stenosis (LTS)-derived fibroblasts. Study Design. Controlled in vitro study. Setting. Tertiary care hospital in a research university. Subjects and Methods. Fibroblasts isolated from biopsies of 5 patients with laryngotracheal stenosis were cultured. Cell proliferation, histology, gene expression, and cellular metabolism of LTS-derived fibroblasts were assessed in 4 conditions: (1) fibroblast growth medium, (2) fibroblast growth medium with dimethylsulfoxide (DMSO), (3) fibroblast growth medium with 10-10 M (low-dose) rapamycin dissolved in DMSO, and (4) fibroblast growth medium with 10-9 M (high-dose) rapamycin dissolved in DMSO. Results. The LTS fibroblast count and DNA concentration were reduced after treatment with high-dose rapamycin compared to DMSO (P = .0007) and normal (P = .0007) controls. Collagen I expression decreased after treatment with highdose rapamycin versus control (P = .0051) and DMSO (P = .0093) controls. Maximal respiration decreased to 68.6 pMoles of oxygen/min/10 mg/protein from 96.9 for DMSO (P = .0002) and 97.0 for normal (P = .0022) controls. Adenosine triphosphate (ATP) production decreased to 66.8 pMoles from 88.1 for DMSO (P = .0006) and 83.3 for normal (P = .0003) controls. Basal respiration decreased to 78.6 pMoles from 108 for DMSO (P = .0002) and 101 for normal (P = .0014) controls. Conclusions. Rapamycin demonstrated an anti-fibroblast effect by significantly reducing the proliferation, metabolism, and collagen deposition of human LTS fibroblast in vitro. Rapamycin significantly decreased oxidative phosphorylation of LTS fibroblasts, suggesting at a potential mechanism for the reduced proliferation and differentiation. Furthermore, rapamycin's anti-fibroblast effects indicate a promising adjuvant therapy for the treatment of laryngotracheal stenosis.

Original languageEnglish (US)
Pages (from-to)881-888
Number of pages8
JournalOtolaryngology - Head and Neck Surgery (United States)
Volume152
Issue number5
DOIs
StatePublished - May 9 2015

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Keywords

  • collagen
  • fibroblasts
  • human
  • laryngotracheal stenosis
  • rapamycin
  • trachea

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

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