Selective regulation of the activity of different hematopoietic regulatory
proteins by transforming growth factor beta 1 in normal and leukemic
myeloid cells
J Lotem and L Sachs
Department of Molecular Genetics and Virology, Weizmann Institute of
Science, Rehovot, Israel.
The viability of normal bone marrow myeloid precursor cells induced by
interleukin-6 (IL-6) or IL-1 alpha and the ability of IL-6 and IL-1 alpha
to induce the formation of colonies of granulocytes, macrophages, or
megakaryocytes in densely seeded bone marrow cultures was suppressed by
transforming growth factor-beta 1 (TGF-beta 1). Induction of normal bone
marrow colony formation by IL-3 was much less sensitive to TGF- beta 1, and
there was little or no effect of TGF-beta 1 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-beta 1
suppressed differentiation induced with IL- 6, IL-1 alpha, or
lipopolysaccharide (LPS), but did not suppress differentiation induced with
IL-3 or GM-CSF. The effect of TGF-beta 1 on differentiation of the leukemic
cells can be dissociated from its effect on cell growth. TGF-beta 1
suppressed the production of IL-6 in normal bone marrow cells cultured with
IL-1 alpha and the production of IL-6 and GM-CSF in leukemic cells cultured
with IL-1 alpha or LPS. The suppression of IL-6 production can explain the
suppression by TGF-beta 1 of the effects of IL-1 alpha and LPS that are
mediated by IL-6. TGF- beta 1 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-beta 1 suppressed or enhanced induction of differentiation with
dexamethasone. The results show that TGF-beta 1 can selectively control the
activity of different molecular regulators of normal and leukemic
hematopoiesis.
Volume 76,
Issue 7,
pp. 1315-1322,
10/01/1990
Copyright © 1990 by The American Society of Hematology