Doxycycline inhibits TGF-1-induced extracellular matrix production in nasal polyp-derived fibroblasts
- Authors
- Shin, Jae-Min; Park, Joo-Hoo; Park, Il-Ho; Lee, Heung-Man
- Issue Date
- 3월-2016
- Publisher
- WILEY
- Keywords
- nasal polyp; fibroblast; extracellular matrix; TGF-1; doxycycline; MAPK; NF-B
- Citation
- INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY, v.6, no.3, pp.256 - 263
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
- Volume
- 6
- Number
- 3
- Start Page
- 256
- End Page
- 263
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/89299
- DOI
- 10.1002/alr.21660
- ISSN
- 2042-6976
- Abstract
- BackgroundDoxycycline 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)-1-induced myofibroblast differentiation and extracellular matrix production in nasal polyp-derived fibroblasts (NPDFs). We also determined the molecular mechanisms of action for doxycycline. MethodsNPDFs were isolated from nasal polyps from 8 patients. Doxycycline was used to pretreat TGF-1-induced NPDFs. Cytotoxicity was evaluated using a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Expression levels of -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-B activation were determined using Western blot analysis. Luciferase assay was used to evaluate the transcriptional activity of NF-B. ResultsAlthough doxycycline (0 to 40g/mL) had no significant cytotoxic effects in TGF-1-induced NPDFs, it significantly reduced the expression levels of -SMA, fibronectin, and collagen in TGF-1-induced NPDFs in a dose-dependent manner. Doxycycline also inhibited the TGF-1-induced activation of p38, c-Jun NH2-terminal kinase (JNK), and NF-B, and its inhibitory effects were similar to those of the specific inhibitors for each. ConclusionDoxycycline has an inhibitory effect on TGF-1-induced myofibroblast differentiation and extracellular matrix production via the p38 and JNK/NF-B signal pathways in NPDFs.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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