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

Hideaki Nakajima, Masahiro Kizaki, Akira Sonoda, Shigehisa Mori, Kenichi Harigaya, Yasuo Ikeda

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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)-α and retinoid X receptor (RXR)-α were expressed constitutively in KM101 cells. ATRA did not affect the expression of either receptor, whereas 9-cis RA increased RXR-α mRNA expression in a dose-dependent manner, but did not affect levels of RAR-α 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).

Original languageEnglish
Pages (from-to)4107-4115
Number of pages9
JournalBlood
Volume84
Issue number12
Publication statusPublished - 1994 Dec 15

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Macrophage Colony-Stimulating Factor
Macrophages
Retinoids
Granulocyte-Macrophage Colony-Stimulating Factor
Tretinoin
Mesenchymal Stromal Cells
Bone
Retinoid X Receptors
Retinoic Acid Receptors
Hematopoiesis
Cytokines
Messenger RNA
alitretinoin
Cells
Cell Line
Acute Promyelocytic Leukemia
Stereoisomerism
Therapeutic Uses
Acute Myeloid Leukemia

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Nakajima, Hideaki; Kizaki, Masahiro; Sonoda, Akira; Mori, Shigehisa; Harigaya, Kenichi; Ikeda, Yasuo.

In: Blood, Vol. 84, No. 12, 15.12.1994, p. 4107-4115.

Research output: Contribution to journalArticle

Nakajima, Hideaki ; Kizaki, Masahiro ; Sonoda, Akira ; Mori, Shigehisa ; Harigaya, Kenichi ; Ikeda, Yasuo. / 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. In: Blood. 1994 ; Vol. 84, No. 12. pp. 4107-4115.
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