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Transforming growth factor‐β1 enhances the suppression of human hematopoiesis by tumor necrosis factor‐α or recombinant interferon‐α
Author(s) -
Sing Garwin K.,
Keller Jonathan R.,
Ellingsworth Larry R.,
Ruscetti Francis W.
Publication year - 1989
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240390203
Subject(s) - transforming growth factor , tumor necrosis factor alpha , haematopoiesis , cytokine , interferon , hematopoietic growth factor , progenitor cell , growth factor , biology , granulocyte macrophage colony stimulating factor , stem cell factor , cancer research , immunology , endocrinology , medicine , stem cell , microbiology and biotechnology , receptor
Abstract The effects of transforming growth factor‐β1 (TGF‐β1) on human hematopoiesis were evaluated in combination with two other regulatory cytokines, namely, recombinant human tumor necrosis factor‐α (TNF‐α) and recombinant human interferon‐α (rIFN‐α). Combinations of TNF‐α and TGF‐β1 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‐β1 synergized with rIFN‐α to suppress CFU‐GM formation, while the combined suppressive effects of both cytokines on CFU‐GEMM and BFU‐E were additive. When TGF‐β1 was tested with TNF‐α or IFN‐α on granulocyte/macrophage colony‐stimulating factor (GM‐CSF)‐stimulated bone marrow cells in a 5‐day proliferation assay, the antiproliferative effects of TGF‐β1 and TNF‐α were additive, while those with TGF‐β1 and rIFN‐α were synergistic. A similar pattern was seen in the suppression of the myeloblastic cell line KG‐1 where TGF‐β1 in combination with TNF‐α resulted in an additive suppression while inhibition by TGF‐β1 and IFN‐α was synergistic. These results demonstrate for the first time the cooperative effects between TGF‐β and TNF‐α and IFN‐α in the suppression of hematopoietic cell growth, raising the possibility that TGF‐β might be used in concert with TNF‐α or IFN‐α in the treatment of various myeloproliferative disorders.