Doxycycline inhibits TGF‐β1–induced extracellular matrix production in nasal polyp–derived fibroblasts. Issue 3 (17th November 2015)

• Record Type: Journal Article
• Authors: Shin, Jae‐Min; Park, Joo‐Hoo; Park, Il‐Ho; Lee, Heung‐Man
• Is Part Of: International forum of allergy & rhinology. Volume 6:Issue 3(2016:Feb.)
• Page Start: 256
• Page End: 263
• Publication Date: 2015-11-17
• Subjects: nasal polyp -- fibroblast -- extracellular matrix -- TGF‐β1 -- doxycycline -- MAPK -- NF‐κB; 617.51005
• DOI: 10.1002/alr.21660
• Languages: English
• ISSNs: 2042-6976

Abstract

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.