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Regulation of release of hepatocyte growth factor from human promyelocytic
leukemia cells, HL-60, by 1,25-dihydroxyvitamin D3, 12-O-
tetradecanoylphorbol 13-acetate, and dibutyryl cyclic adenosine
monophosphate
M Inaba, H Koyama, M Hino, S Okuno, M Terada, Y Nishizawa, T Nishino and H Morii
Second Department of Internal Medicine, Osaka City University Medical
School, Japan.
Hepatocyte growth factor (HGF) secreted from human promyelocytic leukemia
cell line, HL-60, is indistinguishable from HGF in human plasma and its
release is significantly stimulated by 12-O-
tetradecanoylphorbol-13-acetate (TPA), a differentiation-inducer of HL- 60
cells into monocytes/macrophages (Nishino T et al: Biochem Biophys Res
Commun 181:323, 1991). TPA stimulated HGF release from the cells through an
activation of C-kinase, but not through a formation of reactive oxygen
species. Furthermore, dibutyryl cAMP (dbcAMP), an activator of A-kinase and
granulocyte-inducer, also stimulated HGF release. 1,25-Dihydroxyvitamin D3,
another monocyte/macrophage-inducer, abated either TPA- or
dbcAMP-stimulated synthesis and release of HGF in a dose-dependent manner
probably via its nuclear receptor as reflected by vitamin D analog study.
The effects of these three reagents on the steady-state levels of HGF mRNA
of 6.0 kb corresponded with their effects on its protein levels.
Furthermore, a close correlation between intracellular and extracellular
HGF levels strongly suggested that these reagents affected HGF release
mainly on its synthesis step. Recombinant human HGF significantly
stimulated the proliferation and alkaline phosphatase activity of mouse
osteoblastic cell line, MC3T3- E1. In summary, HL-60 cells secrete HGF,
whose synthesis is specifically regulated by various reagents independent
of their differentiation-inducing effects. Because HGF shows a direct
effect on osteoblast-like cells, it might be involved in the interaction of
bone marrow cells with bone cells.
Volume 82,
Issue 1,
pp. 53-59,
07/01/1993
Copyright © 1993 by The American Society of Hematology
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