title: Transforming growth factor beta induces vascular endothelial growth factor elaboration from pleural mesothelial cells in vivo and in vitro.
abstract: 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 microg), talc (400 mg/kg), doxycycline (10 mg/kg), or buffer intrapleurally. 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 microg of TGF-beta(2) than in those given 1.7 microg 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-beta increases the VEGF production by mesothelial cells in vivo and in vitro.
authors.affiliation: Department of Pulmonary Medicine, St. Thomas Hospital and Vanderbilt University, Nashville, Tennessee 37202, USA. ycgarylee@hotmail.com
authors.forename: Y C
authors.initials: YC
authors.lastname: Gary Lee
authors.forename: Dee
authors.initials: D
authors.lastname: Melkerneker
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Thompson
authors.forename: Richard W
authors.initials: RW
authors.lastname: Light
authors.forename: Kirk B
authors.initials: KB
authors.lastname: Lane
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D016228:Endothelial Growth Factors / Q000502:physiology*; D004848:Epithelium / Q000187:drug effects* / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D007958:Leukocyte Count; D016014:Linear Models; D008222:Lymphokines / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010994:Pleura / Q000166:cytology*; D010996:Pleural Effusion / Q000737:chemistry / Q000166:cytology / Q000188:drug therapy* / Q000209:etiology*; D018700:Pleurodesis / Q000009:adverse effects* / Q000379:methods*; D011506:Proteins / Q000032:analysis; D011817:Rabbits; D013627:Talc / Q000494:pharmacology / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D011506:Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013627:Talc; D007770:L-Lactate Dehydrogenase; D004318:Doxycycline