Induction of hepatocyte growth factor/scatter factor by interferon-γ in human leukemia cells

Induction of hepatocyte growth factor/scatter factor (HGF/SF) may be one of the critical steps in organ regeneration, wound healing, and embryogenesis. We previously reported the production of HGF/SF from various human leukemia cell lines and a high level of the growth factor in blood and bone marrow plasma from patients with various types of leukemia. We determined here the effects of hematopoietic cytokines on HGF/SF production in human leukemia cell lines, KG‐1, a myeloid cell line, and RPMI‐8226, a B cell line. Interferon (IFN)‐γ remarkably stimulated HGF/SF production in both cell lines at concentrations of more than 0.1 or 1 IU/ml. IFN‐α and IFN‐β were as effective as IFN‐γ in RPMI‐8226 cells, but less than IFN‐γ in KG‐1 cells. HGF/SF gene expression in KG‐1 cells was also up‐regulated by IFN‐γ. Granulocyte colony‐stimulating factor (G‐CSF), granulocyte/macrophage colony‐stimulating factor (GM‐CSF), interleukin (IL)‐5 and IL‐6 had no effect on HGF/SF production in the 2 leukemia cell lines. We also determined the effects of HGF/SF inducers known for human fibroblasts on the growth factor production in leukemia cells. Out of phorbol 12‐myristate 13‐acetate (PMA), cholera toxin, IL‐1β, and tumor necrosis factor (TNF)‐α, the former three were as effective as IFN‐γ in KG‐1 cells, but only TNF‐α stimulated HGF/SF production in RPMI‐8226 cells, whose effect was less than those of IFN‐α, IFN‐β, and IFN‐γ. The effect of IFN‐γ in KG‐1 cells was synergistic with that of PMA. In contrast with the effect in leukemia cells, HGF/SF induction by IFN‐γ in human skin fibroblasts was much less than that by PMA or cholera toxin. These results indicated that IFN‐γ is a potent inducer of HGF/SF in human leukemia cells. This finding suggests the presence of a homeostatic control mechanism in liver regeneration and repair: hepatic injury, DNA synthesis inhibition, or apoptosis caused by IFN‐γ is subsequently overcome by cytokine‐induced HGF/SF, a potent promoter of liver DNA synthesis. J. Cell. Physiol. 174:107–114, 1998. © 1998 Wiley‐Liss, Inc.