Korean J Pediatr.  2008 Aug;51(8):879-885. 10.3345/kjp.2008.51.8.879.

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

• Park SU
• Shin JH
• Shim JW
• Kim DS
• Jung HL
• Park MS
• Shim JY

• KMID: 2127996
• DOI: http://doi.org/10.3345/kjp.2008.51.8.879

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.

Keyword

Human lung fibroblast; Transforming growth factor-beta; Vascular endothelial growth factor; Thymus and activation regulated chemokine; Dexamethasone

MeSH Terms

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
Bromodeoxyuridine
Chemokine CCL17
Chemokines
Cytokines
Dexamethasone
Transforming Growth Factor beta
Vascular Endothelial Growth Factor A