scholarly journals Activation of human platelet-derived latent transforming growth factor-β1 by human glioblastoma cells. Comparison with proteolytic and glycosidic enzymes

1991 ◽  
Vol 277 (1) ◽  
pp. 165-173 ◽  
Author(s):  
D Huber ◽  
A Fontana ◽  
S Bodmer
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cultured Cells ◽  
Human Platelets ◽  
Biologically Active ◽  
Beta Activity ◽  
Tgf Beta ◽  
Glioblastoma Cells ◽  
Human Glioblastoma

Transforming growth factor-beta (TGF-beta), a regulator of cell growth and differentiation, is secreted by most cultured cells in latent form (L-TGF-beta). Activation of L-TGF-beta can be achieved by various physico-chemical treatments, including acidification, alkalinization, heating and chaotropic agents. Proposed physiological activators include proteinases and glycosidases, which, however, only lead to limited activation (15-20% of the total TGF-beta activity after acidic activation). In the present study L-TGF-beta 1 partially purified from human platelets was not activated by treatment with neuraminidase or the proteinases plasmin, endoproteinase Arg-C, elastase and chymotrypsin. The mechanism of activation of L-TGF-beta was further assessed by using the human glioblastoma cell line 308, which releases biologically active TGF-beta 2. Factor(s) secreted by 308 glioblastoma cells were found to be able to activate partially purified L-TGF-beta 1 from human platelets. Our finding may prove to constitute a physiologically relevant mechanism for the activation of latent forms of TGF-beta 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.

scholarly journals Type beta transforming growth factor is a potent inhibitor of murine megakaryocytopoiesis in vitro

Blood ◽  
1987 ◽  
Vol 69 (6) ◽  
pp. 1737-1741 ◽  
Author(s):  
T Ishibashi ◽  
SL Miller ◽  
SA Burstein
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Ache Activity ◽  
Transforming Growth Factor ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Significant Inhibition ◽  
Tgf Beta ◽  
Megakaryocytic Differentiation

Abstract To investigate the potential role of platelets in the inhibition of megakaryocytopoiesis, freeze-thawed extracts of human platelets were added to serumless liquid cultures of murine marrow. When acetylcholinesterase (AchE), a marker of megakaryocytic differentiation in mice, was assayed, a significant inhibition of enzymatic activity was noted in cultures containing the equivalent of greater than 5 X 10(6) solubilized platelets per milliliter. Freeze-thawed extracts of granulocytes had significantly less inhibitory effect than did platelets. Transforming growth factor beta (TGF-beta), a growth factor known to be inhibitory to some cell lineages and to be found at relatively high concentrations in platelets, was then added to liquid marrow cultures. A similar inhibition of AchE activity was detected when cultures were stimulated with mitogen-stimulated conditioned medium. The effect was potent with 50% inhibition of AchE activity observed at 4 pmol TGF-beta/L. To determine if TGF-beta inhibited specifically one aspect of megakaryocytic differentiation, the factor was added to isolated single megakaryocytes in serumless culture induced by interleukin 3 (IL3) to increase in size. The number of megakaryocytes increasing in size in response to IL 3 exposure was reduced from 68% to 20% when both factors were simultaneously added to cultures. Colony assays showed that megakaryocytic and granulocyte- macrophage colony detection was inhibited at picomolar concentrations of the factor. These data suggest that TGF-beta is a potent in vitro inhibitor of the murine megakaryocytic lineage, although its effects are not limited to this lineage.

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.

scholarly journals Retinoic acid induces transforming growth factor-beta 2 in cultured keratinocytes and mouse epidermis.

1989 ◽  
Vol 1 (1) ◽  
pp. 87-97 ◽  
Author(s):  
A B Glick ◽  
K C Flanders ◽  
D Danielpour ◽  
S H Yuspa ◽  
M B Sporn
Keyword(s):  
Retinoic Acid ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Biologically Active ◽  
Tgf Beta ◽  
Mouse Epidermis ◽  
Cultured Keratinocytes ◽  
Growth Factor Beta ◽  
Beta 2

We have studied the functional interaction between retinoic acid and transforming growth factor-beta (TGF-beta), using the mouse epidermis as a model system. Treatment with retinoic acid increases expression of TGF-beta 2 in cultured keratinocytes in vitro, as well as in the epidermis in vivo. This TGF-beta 2 is secreted in a biologically active form that can bind to surface receptors, in contrast to most other conditions in which TGF-beta is secreted in a latent form. Specific antibodies to TGF-beta 2 partially reverse the ability of retinoic acid to inhibit DNA synthesis in cultured keratinocytes. The regulation of TGF-beta 2 expression by retinoic acid may have important physiological and pharmacological roles in the maintenance of epidermal homeostasis.

scholarly journals Role of the latent TGF-beta binding protein in the activation of latent TGF-beta by co-cultures of endothelial and smooth muscle cells.

1993 ◽  
Vol 120 (4) ◽  
pp. 995-1002 ◽  
Author(s):  
R Flaumenhaft ◽  
M Abe ◽  
Y Sato ◽  
K Miyazono ◽  
J Harpel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Binding Protein ◽  
Muscle Cells ◽  
Beta Activity ◽  
Dependent Manner ◽  
Tgf Beta

Transforming growth factor beta (TGF-beta) is released from cells in a latent form consisting of the mature growth factor associated with an aminoterminal propeptide and latent TGF-beta binding protein (LTBP). The endogenous activation of latent TGF-beta has been described in co-cultures of endothelial and smooth muscle cells. However, the mechanism of this activation remains unknown. Antibodies to native platelet LTBP and to a peptide fragment of LTBP inhibit in a dose-dependent manner the activation of latent TGF-beta normally observed when endothelial cells are cocultured with smooth muscle cells. Inhibition of latent TGF-beta activation was also observed when cells were co-cultured in the presence of an excess of free LTBP. These data represent the first demonstration of a function for the LTBP in the extracellular regulation of TGF-beta activity and indicate that LTBP participates in the activation of latent TGF-beta, perhaps by concentrating the latent growth factor on the cell surface where activation occurs.

scholarly journals Molecular determinants of transforming growth factor beta-1 action on human glioblastoma cells

2016 ◽  
Vol 3 (2) ◽  
pp. 50-59
Author(s):  
V. E. Shevchenko ◽  
S. V. Kovalev ◽  
N. E. Arnotskaya ◽  
Z. N. Nikiforova ◽  
I. A. Kudryavtsev ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Glioblastoma Cells ◽  
Human Glioblastoma ◽  
Molecular Determinants ◽  
Growth Factor Beta ◽  
Human Glioblastoma Cells

scholarly journals Transforming growth factor-beta activity is potentiated by heparin via dissociation of the transforming growth factor-beta/alpha 2-macroglobulin inactive complex.

1989 ◽  
Vol 109 (1) ◽  
pp. 441-448 ◽  
Author(s):  
T A McCaffrey ◽  
D J Falcone ◽  
C F Brayton ◽  
L A Agarwal ◽  
F G Welt ◽  
...  
Keyword(s):  
Biological Activity ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Biologically Active ◽  
Antiproliferative Effect ◽  
Tgf Beta ◽  
Binding Studies ◽  
Growth Inhibitory ◽  
Growth Factor Beta

The control of smooth muscle cell (SMC) proliferation is determined by the combined actions of mitogens, such as platelet-derived growth factor, and the opposing action of growth inhibitory agents, such as heparin and transforming growth factor-beta (TGF-beta). The present studies identify an interaction between heparin and TGF-beta in which heparin potentiates the biological action of TGF-beta. Using a neutralizing antibody to TGF-beta, we observed that the short term antiproliferative effect of heparin depended upon the presence of biologically active TGF-beta. This effect was observed in rat and bovine aortic SMC and in CCL64 cells, but not in human saphenous vein SMC. Binding studies demonstrated that the addition of heparin (100 micrograms/ml) to medium containing 10% plasma-derived serum resulted in a 45% increase in the specific binding of 125I-TGF-beta to cells. Likewise, heparin induced a twofold increase in the growth inhibitory action of TGF-beta at concentrations of TGF-beta near its apparent dissociation constant. Using 125I-labeled TGF-beta, we demonstrated that TGF-beta complexes with the plasma component alpha 2-macroglobulin, but not with fibronectin. Heparin increases the electrophoretic mobility of TGF-beta apparently by freeing TGF-beta from its complex with alpha 2-macroglobulin. Dextran sulfate, another highly charged antiproliferative molecule, but not chondroitin sulfate or dermatan sulfate, similarly modified TGF-beta's mobility. Relatively high, antiproliferative concentrations of heparin (1-100 micrograms/ml) were required to dissociate the TGF-beta/alpha 2-macroglobulin complex. Thus, it appears that the antiproliferative effect of heparin may be partially attributed to its ability to potentiate the biological activity of TGF-beta by dissociating it from alpha 2-macroglobulin, which normally renders it inactive. We suggest that heparin-like agents may be important regulators of TGF-beta's biological activity.

scholarly journals Type beta transforming growth factor is a potent inhibitor of murine megakaryocytopoiesis in vitro

Blood ◽  
1987 ◽  
Vol 69 (6) ◽  
pp. 1737-1741 ◽  
Author(s):  
T Ishibashi ◽  
SL Miller ◽  
SA Burstein
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Ache Activity ◽  
Transforming Growth Factor ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Significant Inhibition ◽  
Tgf Beta ◽  
Megakaryocytic Differentiation

To investigate the potential role of platelets in the inhibition of megakaryocytopoiesis, freeze-thawed extracts of human platelets were added to serumless liquid cultures of murine marrow. When acetylcholinesterase (AchE), a marker of megakaryocytic differentiation in mice, was assayed, a significant inhibition of enzymatic activity was noted in cultures containing the equivalent of greater than 5 X 10(6) solubilized platelets per milliliter. Freeze-thawed extracts of granulocytes had significantly less inhibitory effect than did platelets. Transforming growth factor beta (TGF-beta), a growth factor known to be inhibitory to some cell lineages and to be found at relatively high concentrations in platelets, was then added to liquid marrow cultures. A similar inhibition of AchE activity was detected when cultures were stimulated with mitogen-stimulated conditioned medium. The effect was potent with 50% inhibition of AchE activity observed at 4 pmol TGF-beta/L. To determine if TGF-beta inhibited specifically one aspect of megakaryocytic differentiation, the factor was added to isolated single megakaryocytes in serumless culture induced by interleukin 3 (IL3) to increase in size. The number of megakaryocytes increasing in size in response to IL 3 exposure was reduced from 68% to 20% when both factors were simultaneously added to cultures. Colony assays showed that megakaryocytic and granulocyte- macrophage colony detection was inhibited at picomolar concentrations of the factor. These data suggest that TGF-beta is a potent in vitro inhibitor of the murine megakaryocytic lineage, although its effects are not limited to this lineage.

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