Pathologic Fibroblasts in Idiopathic Subglottic Stenosis Amplify Local Inflammatory Signals

Robert J. Morrison, Nicolas George Katsantonis, Kevin M. Motz, Alexander Tell Hillel, C. Gaelyn Garrett, James L. Netterville, Christopher T. Wootten, Susan M. Majka, Timothy S. Blackwell, Wonder P. Drake, Alexander Gelbard

Research output: Contribution to journalArticle

Abstract

Objective: To characterize the phenotype and function of fibroblasts derived from airway scar in idiopathic subglottic stenosis (iSGS) and to explore scar fibroblast response to interleukin 17A (IL-17A). Study Design: Basic science. Setting: Laboratory. Subjects and Methods: Primary fibroblast cell lines from iSGS subjects, idiopathic pulmonary fibrosis subjects, and normal control airways were utilized for analysis. Protein, molecular, and flow cytometric techniques were applied in vitro to assess the phenotype and functional response of disease fibroblasts to IL-17A. Results: Mechanistically, IL-17A drives iSGS scar fibroblast proliferation (P <.01), synergizes with transforming growth factor ß1 to promote extracellular matrix production (collagen and fibronectin; P =.04), and directly stimulates scar fibroblasts to produce chemokines (chemokine ligand 2) and cytokines (IL-6 and granulocyte-macrophage colony-stimulating factor) critical to the recruitment and differentiation of myeloid cells (P <.01). Glucocorticoids abrogated IL-17A-dependent iSGS scar fibroblast production of granulocyte-macrophage colony-stimulating factor (P =.02). Conclusion: IL-17A directly drives iSGS scar fibroblast proliferation, synergizes with transforming growth factor ß1 to promote extracellular matrix production, and amplifies local inflammatory signaling. Glucocorticoids appear to partially abrogate fibroblast-dependent inflammatory signaling. These results offer mechanistic support for future translational study of clinical reagents for manipulation of the IL-17A pathway in iSGS patients.

Original languageEnglish (US)
Pages (from-to)107-115
Number of pages9
JournalOtolaryngology - Head and Neck Surgery (United States)
Volume160
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Keywords

  • fibroblast
  • idiopathic subglottis stenosis
  • IL-17
  • IL-17A
  • iSGS
  • laryngotracheal stenosis
  • tracheal stenosis

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

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