PMID- 20715091 OWN - NLM STAT- MEDLINE DCOM- 20100915 LR - 20211020 IS - 1531-4995 (Electronic) IS - 0023-852X (Print) IS - 0023-852X (Linking) VI - 120 IP - 9 DP - 2010 Sep TI - Role of tumor necrosis factor-alpha in wound repair in human vocal fold fibroblasts. PG - 1819-25 LID - 10.1002/lary.21037 [doi] AB - OBJECTIVES/HYPOTHESIS: Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha (0, 0.1, 1, 10, and 100 ng/mL) with and without 10% fetal bovine serum (FBS). hVFF response to TNF-alpha 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-alpha receptor. RESULTS: In 3D Carbylan-GSX, TNF-alpha inhibited hVFF proliferation in a dose-dependent manner. TNF-alpha (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-alpha 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-alpha 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. FAU - Chen, Xia AU - Chen X AD - Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Wisconsin Madison, Madison, Wisconsin 53705-2275, USA. FAU - Thibeault, Susan L AU - Thibeault SL LA - eng GR - R01 DC004336-07/DC/NIDCD NIH HHS/United States GR - R01 DC004336-11/DC/NIDCD NIH HHS/United States GR - R01 DC004336-08/DC/NIDCD NIH HHS/United States GR - R21 DC008428/DC/NIDCD NIH HHS/United States GR - R01 DC004336-10/DC/NIDCD NIH HHS/United States GR - R21 DC008428-01/DC/NIDCD NIH HHS/United States GR - R21 DC008428-02/DC/NIDCD NIH HHS/United States GR - R01 DC004336-13/DC/NIDCD NIH HHS/United States GR - R01 DC004336/DC/NIDCD NIH HHS/United States GR - R01 DC004336-11S1/DC/NIDCD NIH HHS/United States GR - R01 DC004336-09/DC/NIDCD NIH HHS/United States GR - R01 DC4336/DC/NIDCD NIH HHS/United States GR - R01 DC004336-06/DC/NIDCD NIH HHS/United States GR - R01 DC004336-12A1/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Laryngoscope JT - The Laryngoscope JID - 8607378 RN - 0 (Collagen Type I) RN - 0 (Collagen Type II) RN - 0 (Fibronectins) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Tissue Inhibitor of Metalloproteinase-3) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (carbylan-GSX) RN - 9000-70-8 (Gelatin) RN - 9004-61-9 (Hyaluronic Acid) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Cell Division/drug effects/physiology MH - Cells, Cultured MH - Collagen Type I/analysis MH - Collagen Type II/analysis MH - Fibroblasts/drug effects/*physiology MH - Fibronectins/analysis MH - Gelatin/pharmacology MH - Humans MH - Hyaluronic Acid/analogs & derivatives/pharmacology MH - In Vitro Techniques MH - Matrix Metalloproteinase 1/analysis MH - Matrix Metalloproteinase 2/analysis MH - Receptors, Tumor Necrosis Factor/analysis MH - Tissue Inhibitor of Metalloproteinase-3/analysis MH - Tumor Necrosis Factor-alpha/pharmacology/*physiology MH - Vocal Cords/drug effects/*physiology MH - Wound Healing/drug effects/*physiology PMC - PMC2965638 MID - NIHMS244288 EDAT- 2010/08/18 06:00 MHDA- 2010/09/17 06:00 PMCR- 2011/09/01 CRDT- 2010/08/18 06:00 PHST- 2010/08/18 06:00 [entrez] PHST- 2010/08/18 06:00 [pubmed] PHST- 2010/09/17 06:00 [medline] PHST- 2011/09/01 00:00 [pmc-release] AID - 10.1002/lary.21037 [doi] PST - ppublish SO - Laryngoscope. 2010 Sep;120(9):1819-25. doi: 10.1002/lary.21037.