Transforming Growth Factor-beta Suppresses Proliferation of Rabbit Corneal Endothelial Cells In Vitro

1999 ◽  
Vol 19 (4) ◽  
pp. 327-334 ◽  
Author(s):  
Deshea L. Harris ◽  
Nancy C. Joyce
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Corneal Endothelial Cells ◽  
Growth Factor Beta

scholarly journals Transforming growth factor-beta 1 modulates basic fibroblast growth factor-induced proteolytic and angiogenic properties of endothelial cells in vitro.

1990 ◽  
Vol 111 (2) ◽  
pp. 743-755 ◽  
Author(s):  
M S Pepper ◽  
D Belin ◽  
R Montesano ◽  
L Orci ◽  
J D Vassalli
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Lumen Formation ◽  
Growth Factor Beta ◽  
Pai 1

Tightly controlled proteolytic degradation of the extracellular matrix by invading microvascular endothelial cells is believed to be a necessary component of the angiogenic process. We have previously demonstrated the induction of plasminogen activators (PAs) in bovine microvascular endothelial (BME) cells by three agents that induce angiogenesis in vitro: basic FGF (bFGF), PMA, and sodium orthovanadate. Surprisingly, we find that these agents also induce plasminogen activator inhibitor-1 (PAI-1) activity and mRNA in BME cells. We also find that transforming growth factor-beta 1 (TGF-beta 1), which in vitro modulates a number of endothelial cell functions relevant to angiogenesis, also increases both PAI-1 and urokinase-type PA (u-PA) mRNA. Thus, production of both proteases and protease inhibitors is increased by angiogenic agents and TGF-beta 1. However, the kinetics and amplitude of PAI-1 and u-PA mRNA induction by these agents are strikingly different. We have used the ratio of u-PA:PAI-1 mRNA levels as an indicator of proteolytic balance. This ratio is tilted towards enhanced proteolysis in response to bFGF, towards antiproteolysis in response to TGF-beta 1, and is similar to that in untreated cultures when the two agents are added simultaneously. Using an in vitro angiogenesis assay in three-dimensional fibrin gels, we find that TGF-beta 1 inhibits the bFGF-induced formation of tube-like structures, resulting in the formation of solid endothelial cell cords within the superficial parts of the gel. These results suggest that a net positive proteolytic balance is required for capillary lumen formation. A novel perspective is provided on the relationship between extracellular matrix invasion, lumen formation, and net proteolytic balance, thereby reflecting the interplay between angiogenesis-modulating cytokines such as bFGF and TGF-beta 1.

scholarly journals Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.

1991 ◽  
Vol 173 (3) ◽  
pp. 589-597 ◽  
Author(s):  
G Poli ◽  
A L Kinter ◽  
J S Justement ◽  
P Bressler ◽  
J H Kehrl ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Growth Factor ◽  
Cell Line ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Immunodeficiency Virus ◽  
Growth Factor Beta

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.

In vitro modulation of endothelial fenestrae: opposing effects of retinoic acid and transforming growth factor beta

1988 ◽  
Vol 91 (2) ◽  
pp. 313-318
Author(s):  
T. Lombardi ◽  
R. Montesano ◽  
M.B. Furie ◽  
S.C. Silverstein ◽  
L. Orci
Keyword(s):  
Endothelial Cells ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Surface Density ◽  
Transforming Growth Factor ◽  
Control Cell ◽  
Tgf Beta ◽  
Growth Factor Beta

Cultured endothelial cells isolated from fenestrated capillaries express many properties characteristic of their in vivo differentiated phenotype, including the formation of a limited number of fenestrae. In this study, we have investigated whether physiological factors that control cell differentiation might regulate the surface density of fenestrae in capillary endothelial cells. We have found that treatment of the cultures with retinoic acid (10 microM) induces a more than threefold increase in the surface density of endothelial fenestrae, whereas transforming growth factor beta (TGF beta) (2 ng ml-1) causes a sevenfold decrease in the surface density of these structures. These results show that the expression of endothelial fenestrae is susceptible to bidirectional modulation by physiological signals, and suggest that retinoids and TGF beta may participate in the regulation of fenestral density of capillary endothelium in vivo.

scholarly journals Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia.

1991 ◽  
Vol 173 (5) ◽  
pp. 1121-1132 ◽  
Author(s):  
R A Fava ◽  
N J Olsen ◽  
A E Postlethwaite ◽  
K N Broadley ◽  
J M Davidson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Synovial Tissue ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Biologically Active ◽  
Tgf Beta ◽  
Histological Techniques ◽  
Growth Factor Beta

We have studied the consequences of introducing human recombinant transforming growth factor beta 1 (hrTGF-beta 1) into synovial tissue of the rat, to begin to better understand the significance of the fact that biologically active TGF-beta is found in human arthritic synovial effusions. Within 4-6 h after the intra-articular injection of 1 microgram of hrTGF-beta 1 into rat knee joints, extensive recruitment of polymorphonuclear leukocytes (PMNs) was observed. Cytochemistry and high resolution histological techniques were used to quantitate the influx of PMNs, which peaked 6 h post-injection. In a Boyden chamber assay, hrTGF-beta 1 at 1-10 fg/ml elicited a chemotactic response from PMNs greater in magnitude than that evoked by FMLP, establishing that TGF-beta 1 is an effective chemotactic agent for PMNs in vitro as well as in vivo. That PMNs may represent an important source of TGF-beta in inflammatory infiltrates was strongly suggested by a demonstration that stored TGF-beta 1 was secreted during phorbol myristate acetate-stimulated degranulation in vitro. Acid/ethanol extracts of human PMNs assayed by ELISA contained an average of 355 ng of TGF/beta 1 per 10(9) cells potentially available for secretion during degranulation of PMNs. [3H]Thymidine incorporation in vivo and autoradiography of tissue sections revealed that widespread cell proliferation was triggered by TGF-beta 1 injection. Synovial lining cells and cells located deep within the subsynovial connective tissue were identified as sources of at least some of the new cells that contribute to TGF-beta 1-induced hyperplasia. Our results demonstrate that TGF-beta is capable of exerting pathogenic effects on synovial tissue and that PMNs may represent a significant source of the TGF-beta present in synovial effusions.

Expression and secretion of transforming growth factor-beta by bleomycin-stimulated rat alveolar macrophages

1993 ◽  
Vol 264 (1) ◽  
pp. L36-L42 ◽  
Author(s):  
E. M. Denholm ◽  
S. M. Rollins
Keyword(s):  
Growth Factor ◽  
Alveolar Macrophages ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Chemotactic Activity ◽  
Beta Activity ◽  
Dependent Manner ◽  
Tgf Beta ◽  
Growth Factor Beta

Bleomycin-induced fibrosis in rodents has been used extensively as a model of human pulmonary fibrosis. The influx of monocytes observed during the early stages of fibrosis is at least partially regulated by the elaboration of chemotactic factors in the lung. Exposure of alveolar macrophages (AM phi) to bleomycin either in vivo or in vitro stimulated secretion of monocyte chemotactic activity (MCA). This MCA has been previously characterized as being primarily due to fibronectin fragments. The present experiments revealed that bleomycin also induced AM phi to secrete a second chemotactic factor, transforming growth factor-beta (TGF-beta). However, the TGF-beta secreted by macrophages was in latent form, since no TGF-beta activity was detected unless AM phi conditioned medium (CM) was acid-activated. After acidification, chemotactic activity in CM from AM phi stimulated with bleomycin in vitro was increased by 3.6, whereas activity in AM phi CM from fibrotic rats increased by 2 and that of a bleomycin-stimulated AM phi cell line increased by 1.6. This acid-activatable chemotactic activity was inhibited by antibody to TGF-beta. Bleomycin-stimulated AM phi s secreted significantly more TGF-beta than did unstimulated controls. Further, in vitro exposure of AM phi to bleomycin induced TGF-beta mRNA expression in a time- and concentration-dependent manner, with maximal mRNA being detected following a 16-h incubation with 1 microgram/ml bleomycin.

Sign in / Sign up

Export Citation Format

Share Document