Purification of the transforming growth factor-beta (TGF-beta) binding proteoglycan betaglycan.

Analyses of cDNA clones coding for simian type 1 transforming growth factor beta (TGF-beta 1) suggest that there are three potential sites for N-linked glycosylation located in the amino terminus of the precursor region. Analysis of [3H]glucosamine-labeled serum-free supernatants from a line of Chinese hamster ovary cells which secrete high levels of recombinant TGF-beta 1 indicate that the TGF-beta 1 precursor, but not the mature form, is glycosylated. Digestion with neuraminidase resulted in a shift in migration of the two TGF-beta 1 precursor bands, which suggests that they contain sialic acid residues. Endoglycosidase H had no noticeable effect. Treatment with N-glycanase produced two faster-migrating sharp bands, the largest of which had a molecular weight of 39 kilodaltons. TGF-beta 1-specific transcripts produced by SP6 polymerase programmed the synthesis of a 42-kilodalton polypeptide which, we suggest, is the unmodified protein backbone of the precursor. Labeling with 32Pi showed that the TGF-beta 1 precursor was phosphorylated in the amino portion of the molecule.

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

Journal of Experimental Medicine ◽

10.1084/jem.173.3.589 ◽

1991 ◽

Vol 173 (3) ◽

pp. 589-597 ◽

Cited By ~ 109

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.

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Early gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function

Molecular and Cellular Biology ◽

10.1128/mcb.11.10.4952-4958.1991 ◽

1991 ◽

Vol 11 (10) ◽

pp. 4952-4958

Author(s):

A Zentella ◽

F M Weis ◽

D A Ralph ◽

M Laiho ◽

J Massagué

Keyword(s):

Cell Cycle ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Lung Epithelial Cells ◽

Early Gene ◽

Tgf Beta ◽

Suppressive Function ◽

Growth Factor Beta ◽

Pai 1

The growth-suppressive function of the retinoblastoma susceptibility gene product, RB, has been implicated in the mediation of growth inhibition and negative regulation of certain proliferation related genes by transforming growth factor-beta 1 (TGF-beta 1). Early gene responses to TGF-beta 1 were examined in order to determine their dependence on the cell cycle and on the growth-suppressive function of RB. TGF-beta 1, which rapidly elevates the steady-state level of junB and PAI-1 mRNAs and decreases that of c-myc mRNA, induces these responses in S-phase populations of Mv1Lu lung epithelial cells containing RB in a phosphorylated state. Since in this state RB is presumed to lack growth-suppressive activity, the response to TGF-beta 1 was also examined in DU145 human prostate carcinoma cells whose mutant RB product lacks growth-suppressive function. In these cells, TGF-beta 1 also decreases c-myc expression at the transcription initiation level. These results suggests that the c-myc, junB, and PAI-1 responses to TGF-beta 1 are not restricted to the G1 phase of the cell cycle and that down-regulation of c-myc expression by TGF-beta 1 can occur through a mechanism independent from the growth-suppressive function of RB.

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

Journal of Cell Science ◽

10.1242/jcs.91.2.313 ◽

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.

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Cloning of a growth arrest-specific and transforming growth factor beta-regulated gene, TI 1, from an epithelial cell line

Molecular and Cellular Biology ◽

10.1128/mcb.11.10.5338-5345.1991 ◽

1991 ◽

Vol 11 (10) ◽

pp. 5338-5345

Author(s):

B Kallin ◽

R de Martin ◽

T Etzold ◽

V Sorrentino ◽

L Philipson

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Lung Epithelial Cells ◽

Epithelial Cell Line ◽

Type I ◽

Tgf Beta ◽

Protein Synthesis Inhibitors ◽

Plasminogen Activator Inhibitor 1 ◽

Growth Factor Beta

By cDNA cloning and differential screening, five genes that are regulated by transforming growth factor beta (TGF beta) in mink lung epithelial cells were identified. A novel membrane protein gene, TI 1, was identified which was downregulated by TGF beta and serum in quiescent cells. In actively growing cells, the TI 1 gene is rapidly and transiently induced by TGF beta, and it is overexpressed in the presence of protein synthesis inhibitors. It appears to be related to a family of transmembrane glycoproteins that are expressed on lymphocytes and tumor cells. The four other genes were all induced by TGF beta and correspond to the genes of collagen alpha type I, fibronectin, plasminogen activator inhibitor 1, and the monocyte chemotactic cell-activating factor (JE gene) previously shown to be TGF beta regulated.

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

Journal of Experimental Medicine ◽

10.1084/jem.173.5.1121 ◽

1991 ◽

Vol 173 (5) ◽

pp. 1121-1132 ◽

Cited By ~ 129

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.

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Transforming growth factor beta 1 (TGF-beta 1) in the pathophysiology of nasal polyp

The Turkish Journal of Ear Nose and Throat ◽

10.5606/tr-ent.2018.78095 ◽

2018 ◽

Vol 28 (2) ◽

pp. 93-104

Author(s):

Evrim Damcayırı Yeniel

Keyword(s):

Growth Factor ◽

Nasal Polyp ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Tgf Beta ◽

Growth Factor Beta

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Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules

Blood ◽

10.1182/blood.v76.10.1946.bloodjournal76101946 ◽

1990 ◽

Vol 76 (10) ◽

pp. 1946-1955 ◽

Cited By ~ 1

Author(s):

RA Fava ◽

TT Casey ◽

J Wilcox ◽

RW Pelton ◽

HL Moses ◽

...

Keyword(s):

In Situ Hybridization ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Messenger Rna ◽

Transforming Growth Factor ◽

Immunoperoxidase Technique ◽

Storage Site ◽

Tgf Beta ◽

Growth Factor Beta

We have directly demonstrated that megakaryocytes are a major site of synthesis and storage of transforming growth factor-beta 1 (TGF/beta 1) by combined immunohistochemical, immunocytochemical, and in situ hybridization methods. The presence of TGF/beta 1 messenger RNA (mRNA) in mature megakaryocytes in adult rat spleen and bone marrow (BM) was established by in situ hybridization. Localization of TGF/beta 1 protein to intact alpha-granules of megakaryocytes, its putative storage site, was accomplished in glycol-methacrylate embedded porcine BM with an immunoperoxidase technique and light microscopy. The TGF/beta 1 was sequestered in intracytoplasmic granules in a pattern virtually identical to that of another alpha-granule marker protein, fibrinogen. This observation strongly suggests packaging of TGF/beta 1 into this organelle within megakaryocytes. That TGF/beta 1 mRNA was localized to megakaryocytes suggests that the TGF/beta 1 found in the alpha-granules in platelets originates with megakaryocyte synthesis. The alpha-granule localization of TGF/beta 1, as well as fibrinogen, was also demonstrated in isolated platelets at the ultrastructural level by electronmicroscopy (EM) and postembedding colloidal-gold immunocytochemistry, thus directly demonstrating that alpha-granules are the final storage site for TGF/beta 1 in mature platelets.

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Production of monoclonal antibodies that detect Hodgkin's high molecular weight transforming growth factor-beta

Blood ◽

10.1182/blood.v75.12.2434.bloodjournal75122434 ◽

1990 ◽

Vol 75 (12) ◽

pp. 2434-2437

Author(s):

SR Newcom ◽

LH Muth ◽

ET Parker

Keyword(s):

Molecular Weight ◽

Monoclonal Antibodies ◽

Growth Factor ◽

High Molecular Weight ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Antigenic Determinants ◽

Enzyme Linked Immunosorbent Assay ◽

Tgf Beta ◽

Growth Factor Beta

High molecular weight transforming growth factor-beta (TGF beta) is a physiologically active TGF secreted by nodular sclerosing Reed- Sternberg cells. Five monoclonal murine antibodies were prepared that distinguished Hodgkin's TGF beta from platelet-derived TGF beta using an enzyme-linked immunosorbent assay, neutralization of biologic activity, and Western blotting. These monoclonal antibodies directed at unique antigenic determinants (epitopes) of Hodgkin's TGF beta will allow further characterization of the role of Hodgkin's TGF beta in Hodgkin's disease and related entities.

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