Vascular endothelial growth factor (VEGF) increases vascular permeability and is important in pleural effusion formation. In studies using transforming growth factor beta (TGF-beta) to produce pleurodesis, we observed that although TGF-beta was more effective than talc or doxycycline, it induced transient production of large pleural effusions. We hypothesized that TGF-beta stimulates VEGF production in pleural tissues in vivo, and by mesothelial cells in vitro. New Zealand White rabbits (n = 33) were given TGF-beta(2) (1.7 or 5.0 mug), talc (400 mg/kg), doxycycline (10 mg/kg), or buffer intra-pleurally. Pleural fluid was collected at 24 h. Intrapleural injection of TGF-beta(2) induced a dose-dependent increase in VEGF production. The pleural fluid VEGF level was 2-fold higher in rabbits given 5.0 mug of TGF-beta(2) than in those given 1.7 mug of TGF-beta(2) and 3-fold higher than in those given buffer. VEGF levels were higher after the injection of TGF-beta(2) than after administration of talc or doxycycline. The pleural fluid VEGF correlated significantly with the volume of pleural effusions (r = 0.79, p <0.00001). In vitro, TGF-beta(2) stimulated a dose-dependent increase In VEGF production from murine pleural mesothelial cells. At 4 and 24 h, TGF-beta(2), but not talc or doxycycline, induced a significant increase in VEGF, when compared with controls. The mesothelial cell VEGF production was significantly reduced by anti-TGF-beta antibody in the TGF-beta(2), talc, and control (buffer and medium) groups. In conclusion, mesothelial cells are an important source of VEGF. TGF-P increases the VEGF production by mesothelial cells in vivo and in vitro.
|Journal||American Journal of Respiratory and Critical Care Medicine|
|Publication status||Published - 2002|
Lee, G., Melkerneker, D., Thompson, P., Light, R. W., & Lane, K. B. (2002). Transforming Growth Factor Beta Induces Vascular Endothelial Growth Factor Elaboration from Pleural Mesothelial Cells in Vivo and in Vitro. American Journal of Respiratory and Critical Care Medicine, 165, 88-94. https://doi.org/10.1164/ajrccm.165.1.2104006