Selective regulation of the activity of different hematopoietic regulatory proteins by transforming growth factor β1 in normal and leukemic myeloid cells

Abstract

The viability of normal bone marrow myeloid precursor cells induced by interleukin-6 (IL-6) or IL-1α and the ability of IL-6 and IL-1α to induce the formation of colonies of granulocytes, macrophages, or megakaryocytes in densely seeded bone marrow cultures was suppressed by transforming growth factor-β1 (TGF-β1). Induction of normal bone marrow colony formation by IL-3 was much less sensitive to TGF-β1, and there was little or no effect of TGF-β1 on colony formation induced by macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF). In different clones of myeloid leukemic cells, TGF-β1 suppressed differentiation induced with IL-6, IL-1α, or lipopolysaccharide (LPS), but did not suppress differentiation induced with IL-3 or GM-CSF. The effect of TGF-β1 on differentiation of the leukemic cells can be dissociated from its effect on cell growth. TGF-β1 suppressed the production of IL-6 in normal bone marrow cells cultured with IL-1α and the production of IL-6 and GM-CSF in leukemic cells cultured with IL-1α or LPS. The suppression of IL-6 production can explain the suppression by TGF-β1 of the effects of IL-1α and LPS that are mediated by IL-6. TGF-β1 also suppressed differentiation in clones of myeloid leukemic cells induced with differentiation factor/ leukemia inhibitory factor and tumor necrosis factor. In different leukemic clones TGF-β1 suppressed or enhanced induction of differentiation with dexamethasone. The results show that TGF-β1 can selectively control the activity of different molecular regulators of normal and leukemic hematopoiesis. © 1990 by The American Society of Hematology.