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Retinoids (all-trans and 9-cis retinoic acid) stimulate production of
macrophage colony-stimulating factor and granulocyte-macrophage colony-
stimulating factor by human bone marrow stromal cells
H Nakajima, M Kizaki, A Sonoda, S Mori, K Harigaya and Y Ikeda
Division of Hematology and Laboratory Medicine, Keio University School of
Medicine, Tokyo, Japan.
Retinoic acids (RAs) exert pleiotropic effects on cellular growth and
differentiation. All-trans retinoic acid (ATRA) and 9-cis retinoic acid
(9-cis RA), a stereoisomer of ATRA, induce differentiation of leukemic cell
lines and cells from patients with acute myelogenous leukemia (AML) in
vitro. Despite information on the effects of RAs on hematopoietic cells,
little is known about how RAs act on the hematopoietic microenvironment,
especially on bone marrow stromal cells. Based on recent observations that
various cytokines produced mainly by bone marrow stromal cells regulate
hematopoiesis, we analyzed the effects of RAs on cytokine production by
these cells. ATRA or 9-cis RA treatment of human bone marrow stromal cell
line KM101, which produces macrophage colony-stimulating factor (M-CSF) and
granulocyte- macrophage colony-stimulating factor (GM-CSF) constitutively,
enhanced mRNA levels of both cytokines in a dose-dependent manner. Both RAs
also stimulated M-CSF production from primary cultures of human bone marrow
stromal cells. Both retinoic acid receptor (RAR)-alpha and retinoid X
receptor (RXR)-alpha were expressed constitutively in KM101 cells. ATRA did
not affect the expression of either receptor, whereas 9-cis RA increased
RXR-alpha mRNA expression in a dose-dependent manner, but did not affect
levels of RAR-alpha mRNA. These findings may have important biologic
implications for both the role of RAs in hematopoiesis and the therapeutic
effects of ATRA on the hematopoietic microenvironment in patients with
acute promyelocytic leukemia (APL).
Volume 84,
Issue 12,
pp. 4107-4115,
12/15/1994
Copyright © 1994 by The American Society of Hematology
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