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Role of tumor necrosis factor–α in wound repair in human vocal fold fibroblasts
Author(s) -
Chen Xia,
Thibeault Susan L.
Publication year - 2010
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.21037
Subject(s) - tumor necrosis factor alpha , downregulation and upregulation , mmp1 , mmp2 , matrix metalloproteinase , fibronectin , cytokine , wound healing , biology , extracellular matrix , cancer research , endocrinology , medicine , immunology , microbiology and biotechnology , gene expression , biochemistry , gene
Objectives/Hypothesis: Tumor necrosis factor–α (TNF‐α) is an inflammatory cytokine and apoptotic molecule that appears to be a mediator in inflammation and fibrosis. The objective of this investigation was to examine the effects of TNF‐α on 3D Carbylan‐GSX in vitro cultured human vocal fold fibroblasts (hVFFs), to provide insight into the mechanism responsible for the improved vocal fold wound healing that has been previous reported with Carbylan‐GSX treatment. Study Design: In vitro cell culture. Methods: hVFF were cultured in 3D Carbylan‐GSX and on polystyrene with different dosages of TNF‐α (0, 0.1, 1, 10, and 100 ng/mL) with and without 10% fetal bovine serum (FBS). hVFF response to TNF‐α was characterized by morphology, proliferation rates, and gene transcript levels for matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 2 (MMP2), tissue inhibitor of metalloproteinase 3 (TIMP3), collagen I, collagen III, fibronectin, and TNF‐α receptor. Results: In 3D Carbylan‐GSX, TNF‐α inhibited hVFF proliferation in a dose‐dependent manner. TNF‐α (0.1–100 ng/mL) was shown to significantly downregulate TIMP3 and extracellular matrix–related mRNA transcript levels for collagen III and fibronectin and to upregulate MMP1 and MMP2 expression, resulting in increased MMP/TIMP3 ratios. TNF‐α receptor expression was significantly upregulated in Carbylan‐GSX compared to control polystyrene. Responses were more marked in 10% FBS culture. Conclusions: After vocal fold injury, locally injected Carbylan‐GSX can enhance the role of TNF‐α in remodeling the lamina propria layer of the vocal fold, accelerating wound healing. Carbylan‐GSX has potential as a new therapeutic approach that may lead to better treatment of vocal fold wound healing. Laryngoscope, 2010