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Transforming growth factor-β promoted vascular endothelial growth factor release by human lung fibroblasts

Korean Journal of Pediatrics 2008;51(8):879-885.
Published online August 15, 2008.
Transforming growth factor-β promoted vascular endothelial growth factor release by human lung fibroblasts
Sang Uk Park, Joo Hwa Shin, Jae Won Shim, Deok Soo Kim, Hye Lim Jung, Moon Soo Park, Jung Yeon Shim
Department of Pediatrics, Sungkyunkwan University School of Medicine, Seoul, Korea
인간 폐섬유아세포에서 TGF-β 자극에 의한 VEGF 분비
박상욱, 신주화, 심재원, 김덕수, 정혜림, 박문수, 심정연
성균관대학교 의과대학 강북삼성병원 소아청소년과
Correspondence: 
Jung Yeon Shim, Email: jyssim@hotmail.com
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-β (TGF-β), 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-β, and its release was augmented when co-stimulated with PDGF and TGF-β. 2) VEGF release induced by PDGF or TGF-β 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-β 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.
Key Words: Human lung fibroblast, Transforming growth factor-β, Vascular endothelial growth factor, Thymus and


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