All issues > Volume 51(8); 2008

Original Article

Korean J Pediatr. 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 SU Park¹, Joo Hwa JH Shin¹, Jae Won JW Shim¹, Deok Soo DS Kim¹, Hye Lim HL Jung¹, Moon Soo MS Park¹, Jung Yeon JY Shim¹

¹Department of Pediatrics, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence Jung Yeon JY 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.

Keywords :Human lung fibroblast, Transforming growth factor-β, Vascular endothelial growth factor, Thymus and