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Transforming growth factor-β1 enhances the suppression of human hematopoiesis by tumor necrosis factor-α or recombinant interferon-α

✍ Scribed by Garwin K. Sing; Jonathan R. Keller; Larry R. Ellingsworth; Francis W. Ruscetti


Publisher
John Wiley and Sons
Year
1989
Tongue
English
Weight
439 KB
Volume
39
Category
Article
ISSN
0730-2312

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✦ Synopsis


The effects of transforming growth factor-01 (TGF-01) on human hematopoiesis were evaluated in combination with two other regulatory cytokines, namely, recombinant human tumor necrosis factor-a! (TNF-a) and recombinant human interferon-a (rIFN-a). Combinations of TNF-a and TGF-01 resulted in a synergistic suppression of colony formation by erythroid progenitor cells (BFU-E) and an additive suppression of granulocyte-macrophage (CFU-GM) and multipotential (CFU-GEMM) progenitor cells. In addition, TGF-01 synergized with rIFN-a to suppress CFU-GM formation, while the combined suppressive effects of both cytokines on CFU-GEMM and BFU-E were additive. When TGF-01 was tested with TNF-a or IFN-a on granulocyte/macrophage colony-stimulating factor (GM-CSF)-stimulated bone marrow cells in a 5-day proliferation assay, the antiproliferative effects of TGF-01 and TNF-a were additive, while those with TGF-01 and rIFN-a were synergistic. A similar pattern was seen in the suppression of the myeloblastic cell line KG-1 where TGF-01 in combination with TNF-a resulted in an additive suppression while inhibition by TGF-01 and IFN-a was synergistic.

These results demonstrate for the first time the cooperative effects between TGF-0 and TNF-a and IFN-a in the suppression of hematopoietic cell growth, raising the possibility that TGF-0 might be used in concert with TNF-a or IFN-a in the treatment of various myeloproliferative disorders.


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