Transforming growth factor-beta promoted vascular endothelial growth factor release by human lung fibroblasts.
10.3345/kjp.2008.51.8.879
- Author:
Sang Uk PARK
1
;
Joo Hwa SHIN
;
Jae Won SHIM
;
Deok Soo KIM
;
Hye Lim JUNG
;
Moon Soo PARK
;
Jung Yeon SHIM
Author Information
1. Department of Pediatrics, Sungkyunkwan University School of Medicine, Seoul, Korea. jyssim@hotmail.com
- Publication Type:Original Article
- Keywords:
Human lung fibroblast;
Transforming growth factor-beta;
Vascular endothelial growth factor;
Thymus and activation regulated chemokine;
Dexamethasone
- MeSH:
Airway Remodeling;
Blood Platelets;
Bromodeoxyuridine;
Cell Proliferation;
Chemokine CCL17;
Chemokines;
Coculture Techniques;
Cytokines;
Dexamethasone;
Edema;
Enzyme-Linked Immunosorbent Assay;
Fibroblasts;
Humans;
Lung;
Myocytes, Smooth Muscle;
Transforming Growth Factor beta;
Vascular Endothelial Growth Factor A
- From:Korean Journal of Pediatrics
2008;51(8):879-885
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: The human lung fibroblast may act as an immunomodulatory cell by providing pro-inflammatory cytokines and chemokines, which are important in airway remodeling. Vascular endothelial growth factor (VEGF) induces mucosal edema and angiogenesis. Thymus and activation regulated chemokine (TARC) induces selective migration of T helper 2 cells. We investigated whether human lung fibroblasts produced VEGF and TARC, and the effects were augmented with the co-culture of fibroblasts and human bronchial smooth muscle cells (HBSMC), and whether dexamethasone can inhibit the proliferation and the release of VEGF in lung fibroblasts. METHODS: Human lung fibroblasts were cultured with and without HBSMC, growth-arrested in serum-deprived medium, and pretreated with dexamethasone for 16 hours. After 24-hour stimulation with platelet derived growth factor-BB (PDGF-BB) and/or transforming growth factor-beta (TGF-beta), culture supernatant was harvested for assays of VEGF and TARC. Cell proliferation was assayed using BrdU cell proliferation ELISA kit. RESULTS: 1) The release of VEGF was significantly increased after stimulation with TGF-beta, and its release was augmented when co-stimulated with PDGF and TGF-beta. 2) VEGF release induced by PDGF or TGF-beta was inhibited by dexamethasone. 3) There was no synergistic effect on the release of VEGF when human lung fibroblasts were co-cultured with HBSMC. 4) Dexamethasone did not suppress human lung fibroblasts proliferations. 5) Neither TGF-beta nor PDGF induced TARC release from lung fibroblasts. CONCLUSION: Human lung fibroblasts may modulate airway remodeling by release of VEGF, but they have no synergistic effects when co-cultured with HBSMC. Dexamethasone suppresses VEGF release, not proliferation of lung fibroblast.