Transforming growth factor beta (TGF-beta), a potent inhibitor of erythropoiesis: neutralizing TGF-beta antibodies show erythropoietin as a potent stimulator of murine burst-forming unit erythroid colony formation in the absence of a burst-promoting activity

Abstract Transforming growth factor beta (TGF-beta) is a bifunctional regulator of the growth of myeloid progenitors and is here demonstrated to directly inhibit the growth of primitive erythroid progenitors by 95% to 100% regardless of the cytokines stimulating growth. Autocrine TGF- beta production of primitive hematopoietic progenitors has previously been reported. In the present study, a neutralizing TGF-beta antibody (anti-TGF-beta) added to serum-containing cultures, resulted in a 3-, 4- , and 25-fold increase in burst-forming unit erythroid (BFU-E) colony formation in response to interleukin-4 (IL-4) plus erythropoietin (Epo), SCF plus Epo, and IL-11 plus Epo, respectively. The growth of BFU-E progenitors has been suggested to require a burst-promoting activity in addition to Epo. Accordingly, we observed no BFU-E colony formation in serum-containing cultures in response to Epo alone. In contrast, 50 BFU-E colonies were formed when anti-TGF-beta was included in the culture. In serum-free cultures, Epo also stimulated BFU-E colony formation in the absence of other cytokines, whereas anti-TGF- beta had no effect on the number of colonies formed. Quantitation of TGF-beta 1 in serum by an enzyme-linked immunosorbent assay method showed predominantly the presence of precursor (latent) TGF-beta 1, but also showed active TGF-beta 1 at a concentration sufficient to potently inhibit erythroid colony formation. Thus, neutralization of active TGF- beta 1 in serum shows that Epo alone is sufficient to stimulate the growth of murine BFU-E progenitors.

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Transforming growth factor beta (TGF-beta), a potent inhibitor of erythropoiesis: neutralizing TGF-beta antibodies show erythropoietin as a potent stimulator of murine burst-forming unit erythroid colony formation in the absence of a burst-promoting activity

Blood ◽

10.1182/blood.v86.3.949.bloodjournal863949 ◽

1995 ◽

Vol 86 (3) ◽

pp. 949-957 ◽

Cited By ~ 5

Author(s):

I Dybedal ◽

SE Jacobsen

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Colony Formation ◽

Transforming Growth Factor ◽

Interleukin 4 ◽

Assay Method ◽

Enzyme Linked Immunosorbent Assay ◽

Tgf Beta ◽

Erythroid Progenitors ◽

Growth Factor Beta

Transforming growth factor beta (TGF-beta) is a bifunctional regulator of the growth of myeloid progenitors and is here demonstrated to directly inhibit the growth of primitive erythroid progenitors by 95% to 100% regardless of the cytokines stimulating growth. Autocrine TGF- beta production of primitive hematopoietic progenitors has previously been reported. In the present study, a neutralizing TGF-beta antibody (anti-TGF-beta) added to serum-containing cultures, resulted in a 3-, 4- , and 25-fold increase in burst-forming unit erythroid (BFU-E) colony formation in response to interleukin-4 (IL-4) plus erythropoietin (Epo), SCF plus Epo, and IL-11 plus Epo, respectively. The growth of BFU-E progenitors has been suggested to require a burst-promoting activity in addition to Epo. Accordingly, we observed no BFU-E colony formation in serum-containing cultures in response to Epo alone. In contrast, 50 BFU-E colonies were formed when anti-TGF-beta was included in the culture. In serum-free cultures, Epo also stimulated BFU-E colony formation in the absence of other cytokines, whereas anti-TGF- beta had no effect on the number of colonies formed. Quantitation of TGF-beta 1 in serum by an enzyme-linked immunosorbent assay method showed predominantly the presence of precursor (latent) TGF-beta 1, but also showed active TGF-beta 1 at a concentration sufficient to potently inhibit erythroid colony formation. Thus, neutralization of active TGF- beta 1 in serum shows that Epo alone is sufficient to stimulate the growth of murine BFU-E progenitors.

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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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Release of early human hematopoietic progenitors from quiescence by antisense transforming growth factor beta 1 or Rb oligonucleotides.

Journal of Experimental Medicine ◽

10.1084/jem.174.4.925 ◽

1991 ◽

Vol 174 (4) ◽

pp. 925-929 ◽

Cited By ~ 163

Author(s):

J Hatzfeld ◽

M L Li ◽

E L Brown ◽

H Sookdeo ◽

J P Levesque ◽

...

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Colony Formation ◽

Transforming Growth Factor ◽

Inhibitory Effect ◽

Tgf Beta ◽

Hematopoietic Progenitors ◽

Single Cell Culture ◽

Growth Factor Beta ◽

Blocking Antibodies

We have used antisense oligonucleotides to study the roles of transforming growth factor beta (TGF-beta) and the two antioncogenes, retinoblastoma susceptibility (Rb) and p53, in the negative regulation of proliferation of early hematopoietic cells in culture. The antisense TGF-beta sequence significantly enhanced the frequency of colony formation by multi-lineage, early erythroid, and granulomonocytic progenitors, but did not affect colony formation by late progenitors. Single cell culture and limiting dilution analysis indicated that autocrine TGF-beta is produced by a subpopulation of early progenitors. Antisense Rb but not antisense p53 yielded similar results in releasing multipotential progenitors (colony-forming unit-granulocyte/erythroid/macrophage/megakaryocyte) from quiescence. Rb antisense could partially reverse the inhibitory effect of exogenous TGF-beta. Anti-TGF-beta blocking antibodies, antisense TGF-beta, or Rb oligonucleotides all had similar effects. No additive effects were observed when these reagents were combined, suggesting a common pathway of action. Our results are consistent with the model that autocrine production of TGF-beta negatively regulates the cycling status of early hematopoietic progenitors through interaction with the Rb gene product.

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

Blood ◽

10.1182/blood.v75.12.2434.2434 ◽

1990 ◽

Vol 75 (12) ◽

pp. 2434-2437 ◽

Cited By ~ 2

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

Abstract 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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Transforming growth factor-beta (TGF-beta) isoforms in rat liver regeneration: messenger RNA expression and activation of latent TGF-beta.

Cell Regulation ◽

10.1091/mbc.2.7.535 ◽

1991 ◽

Vol 2 (7) ◽

pp. 535-548 ◽

Cited By ~ 108

Author(s):

S B Jakowlew ◽

J E Mead ◽

D Danielpour ◽

J Wu ◽

A B Roberts ◽

...

Keyword(s):

Extracellular Matrix ◽

Growth Factor ◽

Liver Regeneration ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Enzyme Linked Immunosorbent Assay ◽

Regenerating Liver ◽

Tgf Beta ◽

Extracellular Matrix Components ◽

Growth Factor Beta

Expression of transforming growth factor-beta s (TGF-beta s) 1-3 was studied in normal liver and during liver regeneration after partial hepatectomy in the rat to determine whether each of these isoforms might be involved in hepatocyte growth in vivo. Expression of the mRNAs for all three TGF-beta isoforms increases in the regenerating liver. In addition, the levels of expression of the mRNAs for several extracellular matrix proteins, including fibronectin, vitronectin, laminin, and collagen, also increase in the regenerating liver. Immunohistochemical staining analysis shows a similar distribution of all three TGF-beta s in normal and regenerating liver; however, in both tissues, the level of expression of TGF-beta 1 is 8- to 10-fold higher than that of TGF-beta 2 as determined by sandwich enzyme-linked immunosorbent assay. Expression of all three TGF-beta mRNAs is restricted to liver nonparenchymal cells. Although hepatocytes from normal and regenerating livers do not synthesize TGF-beta, they are sensitive to inhibition of growth by all three TGF-beta isoforms. Hepatocytes from regenerating livers are capable of activating latent TGF-beta 1 complexes in vitro, whereas normal hepatocytes are not. The different TGF-beta isoforms may function in an inhibitory paracrine mechanism that is activated during liver regeneration and may also regulate the synthesis of extracellular matrix components in the regenerating liver.

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Possible Role of Transforming Growth Factor Beta and Interleukin-4 in the Up-Regulation of CLC-2 and CLC-3 in Chronic Rhinosinusitis

American Journal of Rhinology ◽

10.2500/ajr.2007.21.3045 ◽

2007 ◽

Vol 21 (4) ◽

pp. 389-394 ◽

Cited By ~ 6

Author(s):

Huabin Li ◽

Hongyan Jiang ◽

Lei Cheng ◽

Yun Oh ◽

Geng Xu

Keyword(s):

Growth Factor ◽

Chronic Rhinosinusitis ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Ethmoid Sinus ◽

Interleukin 4 ◽

Enzyme Linked Immunosorbent Assay ◽

Tgf Beta ◽

Disease Entities

Background Chronic rhinosinusitis (CRS) may cover different disease entities, and the pathogenic mechanism remains unclear. Methods The aim of this study was to evaluate the expression of chloride channel protein CLC-2 and CLC-3 in CRS without nasal polyps (CRSsNP) and evaluate the roles of interleukin (IL)-4 and transforming growth factor (TGF) beta in the up-regulation of CLC-2 and CLC-3. We detected expression of CLC-2 and CLC-3 in 17 patients with CRSsNP by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and we examined the concentration of TGF-beta, IL-4, IL-5, and interferon (IFN) γ in ethmoid sinus mucosa by enzyme-linked immunosorbent assay (ELISA). Results We found that CLC-2 and CLC-3 is up-regulated in CRSnNP and located in submucosal glands and epithelium of the ethmoid sinus. CLC-2 and CLC-3 mRNA correlated with IL-4 in CRSsNP (r = 0.57 and 0.65; p < 0.05). CLC-2 and CLC-3 mRNA correlated negatively with mucosal TGF-beta in CRSsNP (r = -0.49 and -0.54; p < 0.05). Conclusion We concluded that CLC-2 and CLC-3 is up-regulated in ethmoid mucosa and may affect the development of CRSsNP. TGF-beta and IL-4 may modulate the expression of CLC-2 and CLC-3 in CRSsNP.

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Biased distribution of recombination sites within S regions upon immunoglobulin class switch recombination induced by transforming growth factor beta and lipopolysaccharide.

Journal of Experimental Medicine ◽

10.1084/jem.175.6.1539 ◽

1992 ◽

Vol 175 (6) ◽

pp. 1539-1546 ◽

Cited By ~ 36

Author(s):

T Iwasato ◽

H Arakawa ◽

A Shimizu ◽

T Honjo ◽

H Yamagishi

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Immunoglobulin A ◽

Interleukin 4 ◽

Tgf Beta ◽

Class Switch ◽

Donor And Acceptor ◽

Circular Dnas ◽

Growth Factor Beta

We have characterized extrachromosomal circular DNAs from adult mouse spleen cells that were induced to switch to immunoglobulin A (IgA) with bacterial lipopolysaccharide (LPS) and transforming growth factor beta (TGF-beta), and identified breakpoints of S mu/S gamma 3, S mu/S gamma 2, S mu/S alpha, S gamma 3/S alpha, and S gamma 2/S alpha recombinants. The S mu recombination donor sites clustered in the 3' half of the S mu region, while the S alpha recombination acceptor sites clustered in the 5' half of the S alpha region. In addition, donor and acceptor sites of S gamma regions also clustered in the 3' and 5' parts, respectively. These site preferences are in sharp contrast to the dispersed distribution of S mu/S gamma 1 breakpoints within both S mu and S gamma 1 regions upon IgG1 switch induced by LPS and interleukin 4. Our results support the hypotheses that TGF-beta increases the frequency of switch recombination events to IgA and that the switch recombination to IgA often proceeds by successive recombination of S mu/S gamma and S gamma/S alpha.

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