PMID- 9397161 OWN - NLM STAT- MEDLINE DCOM- 19971230 LR - 20081121 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 174 IP - 1 DP - 1998 Jan TI - Induction of hepatocyte growth factor/scatter factor by interferon-gamma in human leukemia cells. PG - 107-14 AB - 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)-gamma remarkably stimulated HGF/SF production in both cell lines at concentrations of more than 0.1 or 1 IU/ml. IFN-alpha and IFN-beta were as effective as IFN-gamma in RPMI-8226 cells, but less than IFN-gamma in KG-1 cells. HGF/SF gene expression in KG-1 cells was also up-regulated by IFN-gamma. 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-1 beta, and tumor necrosis factor (TNF)-alpha, the former three were as effective as IFN-gamma in KG-1 cells, but only TNF-alpha stimulated HGF/SF production in RPMI-8226 cells, whose effect was less than those of IFN-alpha, IFN-beta, and IFN-gamma. The effect of IFN-gamma in KG-1 cells was synergistic with that of PMA. In contrast with the effect in leukemia cells, HGF/SF induction by IFN-gamma in human skin fibroblasts was much less than that by PMA or cholera toxin. These results indicated that IFN-gamma 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-gamma is subsequently overcome by cytokine-induced HGF/SF, a potent promoter of liver DNA synthesis. FAU - Gohda, E AU - Gohda E AD - Department of Immunochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Japan. gohda@pheasant.pharm.okayama-u.ac.jp FAU - Takebe, T AU - Takebe T FAU - Sotani, T AU - Sotani T FAU - Nakamura, S AU - Nakamura S FAU - Minowada, J AU - Minowada J FAU - Yamamoto, I AU - Yamamoto I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Gene Expression Regulation, Neoplastic/*drug effects MH - Hepatocyte Growth Factor/*biosynthesis/genetics MH - Humans MH - Interferon-gamma/*pharmacology MH - Leukemia/*metabolism MH - Tumor Cells, Cultured EDAT- 1997/12/16 02:44 MHDA- 2000/06/20 09:00 CRDT- 1997/12/16 02:44 PHST- 1997/12/16 02:44 [pubmed] PHST- 2000/06/20 09:00 [medline] PHST- 1997/12/16 02:44 [entrez] AID - 10.1002/(SICI)1097-4652(199801)174:1<107::AID-JCP12>3.0.CO;2-C [pii] AID - 10.1002/(SICI)1097-4652(199801)174:1<107::AID-JCP12>3.0.CO;2-C [doi] PST - ppublish SO - J Cell Physiol. 1998 Jan;174(1):107-14. doi: 10.1002/(SICI)1097-4652(199801)174:1<107::AID-JCP12>3.0.CO;2-C.