Doxycycline inhibits TGF-β1-induced extracellular matrix production in nasal polyp-derived fibroblasts

Jae Min Shin, Joo Hoo Park, Il Ho Park, Heung Man Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Doxycycline has been shown to have antibacterial and anti-inflammatory effects and suppresses collagen biosynthesis. The purpose of this study was to evaluate the effects of doxycycline on transforming growth factor (TGF)-β1-induced myofibroblast differentiation and extracellular matrix production in nasal polyp-derived fibroblasts (NPDFs). We also determined the molecular mechanisms of action for doxycycline. Methods: NPDFs were isolated from nasal polyps from 8 patients. Doxycycline was used to pretreat TGF-β1-induced NPDFs. Cytotoxicity was evaluated using a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Expression levels of α-smooth muscle actin (SMA) and fibronectin were measured using Western blot, reverse-transcription polymerase chain reaction, and immunofluorescence staining. Total collagen production was analyzed with the Sircol collagen assay, while mitogen-activated protein kinase (MAPK) and NF-κB activation were determined using Western blot analysis. Luciferase assay was used to evaluate the transcriptional activity of NF-κB. Results: Although doxycycline (0 to 40 μg/mL) had no significant cytotoxic effects in TGF-β1-induced NPDFs, it significantly reduced the expression levels of α-SMA, fibronectin, and collagen in TGF-β1-induced NPDFs in a dose-dependent manner. Doxycycline also inhibited the TGF-β1-induced activation of p38, c-Jun NH2-terminal kinase (JNK), and NF-κB, and its inhibitory effects were similar to those of the specific inhibitors for each. Conclusion: Doxycycline has an inhibitory effect on TGF-β1-induced myofibroblast differentiation and extracellular matrix production via the p38 and JNK/NF-κB signal pathways in NPDFs.

Original languageEnglish
Pages (from-to)256-263
Number of pages8
JournalInternational Forum of Allergy and Rhinology
Volume6
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1

Keywords

  • Doxycycline
  • Extracellular matrix
  • Fibroblast
  • MAPK
  • Nasal polyp
  • NF-κB
  • TGF-β1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Otorhinolaryngology

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