scholarly journals Type beta transforming growth factors promote interleukin-3 (IL-3)- dependent differentiation of human basophils but inhibit IL-3-dependent differentiation of human eosinophils

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 634-641 ◽  
Author(s):  
C Sillaber ◽  
K Geissler ◽  
R Scherrer ◽  
R Kaltenbrunner ◽  
P Bettelheim ◽  
...  
Keyword(s):  
Growth Factors ◽  
Culture System ◽  
Transforming Growth Factors ◽  
Tgf Beta ◽  
Ifn Gamma ◽  
Interleukin 3 ◽  
Ifn Alpha ◽  
Beta 2 ◽  
Dependent Growth ◽  
Human Basophils

Abstract Basophils and eosinophils share a common differentiation pathway. Factors regulating terminal commitment toward one cell type, however, have so far not been defined. Interleukin-3 (IL-3) is a potent differentiation factor for both human eosinophils and basophils. In the present study, the effects of various recombinant human (rh) growth regulators on IL-3-dependent growth of eosinophils and basophils were studied in a bone marrow (BM) suspension culture system (normal donors, n = 13). We found that type beta transforming growth factors (TGFs) lead to a significant increase in the absolute numbers of basophils in BM cultures grown in the presence of IL-3 (day 14 of culture; IL-3: 133 +/- 20 v IL-3 + TGF-beta 1: 231 +/- 28 x 10(3)/mL [P less than .01]) and to an increase in the total histamine values (IL-3: 72.6 +/- 22.2 v IL-3 + TGF-beta 1: 142.9 +/- 37.3 ng/mL [P less than .015]) compared with rhIL-3 alone. In contrast, type beta TGFs were found to inhibit the IL-3-dependent growth of eosinophils (IL-3: 170.4 +/- 37.2 v IL-3 + TGF-beta 1: 16.7 +/- 5.2 x 10(3)/mL [P less than .01]) and formation of eosinophil cationic protein in the same culture system. The effect of TGF-beta 1 (and TGF-beta 2) on IL-3-dependent differentiation of basophils and eosinophils was dose- and time-dependent (maximum effects observed with 1 to 10 ng/mL of rhTGF-beta 1 or TGF-beta 2) and could be neutralized by an antibody specific for TGF-beta 1. In contrast to the TGFs, interferon-alpha (IFN-alpha) and IFN-gamma were found to downregulate IL-3-dependent formation of both basophils (IL-3: 167 +/- 33 v IL-3 + IFN-alpha: 67 +/- 25 v IL-3 + IFN-gamma: 65 +/- 33 x 10(3)/mL [P less than .01]) and eosinophils (IL-3: 239 +/- 5 v IL-3 + IFN-alpha: 81 +/- 4 v IL-3 + IFN-gamma: 67 +/- 17 x 10(3)/mL [P less than .05]) in our culture system. Type beta TGFs as well as the IFNs failed to directly induce differentiation of human basophils or eosinophils in the absence of other growth factors. Together, these results show that type beta TGFs and IFNs are potent regulators of cytokine-dependent growth and differentiation of human allergic effector cells.

scholarly journals Type beta transforming growth factors promote interleukin-3 (IL-3)- dependent differentiation of human basophils but inhibit IL-3-dependent differentiation of human eosinophils

Blood ◽  
1992 ◽  
Vol 80 (3) ◽  
pp. 634-641 ◽  
Author(s):  
C Sillaber ◽  
K Geissler ◽  
R Scherrer ◽  
R Kaltenbrunner ◽  
P Bettelheim ◽  
...  
Keyword(s):  
Growth Factors ◽  
Culture System ◽  
Transforming Growth Factors ◽  
Tgf Beta ◽  
Ifn Gamma ◽  
Interleukin 3 ◽  
Ifn Alpha ◽  
Beta 2 ◽  
Dependent Growth ◽  
Human Basophils

Basophils and eosinophils share a common differentiation pathway. Factors regulating terminal commitment toward one cell type, however, have so far not been defined. Interleukin-3 (IL-3) is a potent differentiation factor for both human eosinophils and basophils. In the present study, the effects of various recombinant human (rh) growth regulators on IL-3-dependent growth of eosinophils and basophils were studied in a bone marrow (BM) suspension culture system (normal donors, n = 13). We found that type beta transforming growth factors (TGFs) lead to a significant increase in the absolute numbers of basophils in BM cultures grown in the presence of IL-3 (day 14 of culture; IL-3: 133 +/- 20 v IL-3 + TGF-beta 1: 231 +/- 28 x 10(3)/mL [P less than .01]) and to an increase in the total histamine values (IL-3: 72.6 +/- 22.2 v IL-3 + TGF-beta 1: 142.9 +/- 37.3 ng/mL [P less than .015]) compared with rhIL-3 alone. In contrast, type beta TGFs were found to inhibit the IL-3-dependent growth of eosinophils (IL-3: 170.4 +/- 37.2 v IL-3 + TGF-beta 1: 16.7 +/- 5.2 x 10(3)/mL [P less than .01]) and formation of eosinophil cationic protein in the same culture system. The effect of TGF-beta 1 (and TGF-beta 2) on IL-3-dependent differentiation of basophils and eosinophils was dose- and time-dependent (maximum effects observed with 1 to 10 ng/mL of rhTGF-beta 1 or TGF-beta 2) and could be neutralized by an antibody specific for TGF-beta 1. In contrast to the TGFs, interferon-alpha (IFN-alpha) and IFN-gamma were found to downregulate IL-3-dependent formation of both basophils (IL-3: 167 +/- 33 v IL-3 + IFN-alpha: 67 +/- 25 v IL-3 + IFN-gamma: 65 +/- 33 x 10(3)/mL [P less than .01]) and eosinophils (IL-3: 239 +/- 5 v IL-3 + IFN-alpha: 81 +/- 4 v IL-3 + IFN-gamma: 67 +/- 17 x 10(3)/mL [P less than .05]) in our culture system. Type beta TGFs as well as the IFNs failed to directly induce differentiation of human basophils or eosinophils in the absence of other growth factors. Together, these results show that type beta TGFs and IFNs are potent regulators of cytokine-dependent growth and differentiation of human allergic effector cells.

scholarly journals Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas

1997 ◽  
Vol 75 (12) ◽  
pp. 1753-1760 ◽  
Author(s):  
IE Eder ◽  
A Stenzl ◽  
A Hobisch ◽  
MV Cronauer ◽  
G Bartsch ◽  
...  
Keyword(s):  
Growth Factors ◽  
Transforming Growth Factors ◽  
Human Bladder ◽  
Beta 2 ◽  
Bladder Carcinomas

Elevated Levels of Transforming Growth Factors Beta 2 and Beta 3 in Lambdoid Sutures From Children with Persistent Plagiocephaly

1997 ◽  
Vol 34 (4) ◽  
pp. 331-336 ◽  
Author(s):  
Kant Y. Lin ◽  
Amber A. Nolen ◽  
Thomas J. Gampper ◽  
John A. Jane ◽  
Lynne A. Opperman ◽  
...  
Keyword(s):  
Growth Factors ◽  
Transforming Growth Factors ◽  
Beta 2

The growth inhibitor of African green monkey (BSC-1) cells is transforming growth factors .beta.1 and .beta.2

Biochemistry ◽  
1989 ◽  
Vol 28 (8) ◽  
pp. 3442-3447 ◽  
Author(s):  
John M. McPherson ◽  
Steven J. Sawamura ◽  
Yasushi Ogawa ◽  
Kelly Dineley ◽  
Pedro Carrillo ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Inhibitor ◽  
African Green Monkey ◽  
Transforming Growth Factors ◽  
Green Monkey ◽  
Beta 2

scholarly journals Interleukin-3 is a differentiation factor for human basophils

Blood ◽  
1989 ◽  
Vol 73 (7) ◽  
pp. 1763-1769 ◽  
Author(s):  
P Valent ◽  
G Schmidt ◽  
J Besemer ◽  
P Mayer ◽  
G Zenke ◽  
...  
Keyword(s):  
Histamine Release ◽  
Culture System ◽  
Blue Staining ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Differentiation Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Human Basophils

The effect of recombinant human (rh) cytokines, interleukin-1 alpha (IL- 1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), interleukin-4 (IL- 4), granulocyte/macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), monocyte/macrophage colony stimulating factor (M-CSF), interferon-alpha (IF-alpha), interferon-gamma (IF-gamma), and the tumor necrosis factor-alpha (TNF- alpha) on differentiation and function of metachromatic cells (MCS) was studied. Among all cytokines tested, rh interleukin-3 (rhIL-3) selectively induced a significant formation of MCS (IL-3: 1.1 +/- 0.6 x 10(5) v control: 0.02 +/- 0.15 x 10(5) MCS/mL suspension) and dose dependent increase in formation of intracellular histamine (IL-3, 100 U/mL: 95 +/- 23 ng/mL v control: 1.8 +/- 0.8 ng/mL) in a bone marrow suspension culture system (analyzed on day 14 of culture). Besides MCS, formation of eosinophils was observed in this culture system in the continuous presence of rhIL-3, whereas IL-3 pulse-stimulation for three hours and subsequent exposure to control medium induced growth of MCS but not of eosinophils. By combined immunofluorescence/toluidine blue staining, MCS were found to express a cell surface marker profile that corresponds to the immunological phenotype of peripheral blood basophils (MY-7(CD13)+, VIM12(CD11b)+, VIM2+, MAX1-, MAX24- and YB5B8- ). Furthermore, cultured MCS expressed surface membrane receptors for IgE and could be triggered for nontoxic histamine release by a monoclonal anti-IgE antibody. To evaluate a possible influence of IL-3 on basophil function, studies were extended to freshly obtained blood basophils (healthy volunteers, n = 3). However, like all other cytokines tested, rhIL-3 failed to induce basophil histamine release. Taken together, our studies demonstrate that IL-3 is a differentiation factor for human basophils.

scholarly journals Cell-mediated co-action of transforming growth factors: incubation of type beta with normal rat kidney cells produces a soluble activity that prolongs the ruffling response to type alpha.

1986 ◽  
Vol 102 (4) ◽  
pp. 1230-1234 ◽  
Author(s):  
S E Myrdal ◽  
D R Twardzik ◽  
N Auersperg
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Rat Kidney ◽  
Transforming Growth Factors ◽  
Tgf Beta ◽  
Murine Sarcoma Virus ◽  
Normal Rat ◽  
Sarcoma Virus ◽  
Epidermal Growth ◽  
Murine Sarcoma

Intense, continuous ruffling is a characteristic of many transformed cells, but untransformed cells ruffle intensely only briefly after exposure to growth factors. We reported previously that cells of a normal rat kidney (NRK) cell line transformed by Kirsten murine sarcoma virus secrete their own ruffle-inducing agent(s) that cause sustained ruffling in either themselves or untransformed NRK cells. In the present study, we examined the roles of the transforming growth factors TGF-alpha and TGF-beta in the induction and maintenance of ruffling in untransformed NRK cells and observed the following: TGF-alpha caused a transient epidermal growth factor (EGF)-like response, which could be blocked by prior exposure of cells to EGF or by antiserum directed against the COOH-terminus of TGF-alpha. TGF-beta caused no ruffling and did not itself prolong TGF-alpha ruffling. A new, buffer-soluble (transferable) mediator activity produced by incubation of TGF-beta with NRK cells for 6-h extended the duration of maximal TGF-alpha-induced ruffling by several-fold. This study demonstrates that TGF-alpha alone causes an EGF-like, transient ruffling response, but neither TGF-alpha or TGF-beta alone, nor the two together, cause transformation-associated sustained ruffling. Rather, TGF-alpha acts in concert with a new, TGF-beta-dependent activity. This new activity appears to inhibit normal cellular off-regulation of TGF-alpha-induced ruffling. Inhibition of the cellular off-regulation of a growth factor response could play a key role in the unregulated growth associated with malignancy.

scholarly journals Astrocyte-derived TGF-beta 2 and NGF differentially regulate neural recognition molecule expression by cultured astrocytes.

1991 ◽  
Vol 115 (2) ◽  
pp. 473-484 ◽  
Author(s):  
B Saad ◽  
D B Constam ◽  
R Ortmann ◽  
M Moos ◽  
A Fontana ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Adhesion Molecule ◽  
Interleukin 1 ◽  
Dorsal Root Ganglion Neurons ◽  
Tgf Beta ◽  
Beta 2 ◽  
Ganglion Neurons ◽  
Culture Supernatants ◽  
Recognition Molecule

Because of the importance of neural recognition molecules expressed by glial cells to mediate interactions with neurons, growth factors and cytokines known to be functional during morphogenesis and in diseases of the nervous system were studied for their effects on recognition molecule expression by cultured immature and mature astrocytes from several brain regions. In cultures of immature astrocytes, transforming growth factors-beta 1 (TGF-beta 1) and -beta 2 (TGF-beta 2) and nerve growth factor (NGF) increased expression of the neural adhesion molecule L1, leading to a glia-mediated L1-specific increase in neurite outgrowth of dorsal root ganglion neurons on the astrocyte substrate. L1 expression induced by TGF-beta was inhibited by addition of antibodies to NGF, suggesting that TGF-beta influences L1 expression by modulating production of NGF by astrocytes. TGF-beta 1 and -beta 2 decreased expression of N-CAM by immature astrocytes. Since N-CAM expression was not affected by NGF and antibodies to NGF did not abolish the TGF-beta-induced decrease in N-CAM expression, NGF did not appear to be the mediator for regulating expression of N-CAM. Expression of the adhesion molecule on glia (AMOG) was not affected by any factor. NGF and TGF-beta 2 in latent form, but not TGF-beta 1 were found in the culture supernatants. Addition of interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), platelet-derived growth factor (PDGF), or basic fibroblast growth factor (bFGF) to the cultures did not change recognition molecule expression. REcognition molecule expression by mature astrocytes was not found to be modified by any of the factors tested. In view of the observation that levels of L1 and N-CAM expression correlated with the presence of TGF-beta 2 and NGF in the culture supernatants of immature astrocytes, an autocrine regulatory mechanism for recognition molecule expression by these cells is suggested to play a crucial role in regulation of neuron-glia interactions.

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