Interferon gamma has dual potential in inhibiting or promoting survival and growth of hematopoietic progenitors: interactions with stromal cell-derived factor 1.
We explored the possibility that interferon gamma (IFN-gamma) has bidirectional functions in the survival and growth of hematopoietic progenitors, especially with regard to interactions with stromal cell-derived factor 1 (SDF-1). IFN-gamma partially rescued normal bone marrow CD34+ cells and colony-forming cells from apoptosis induced by serum and hematopoietic growth factor (HGF) deprivation, and SDF-1 further enhanced cell survival. Short-term IFN-gamma treatment of CD34+ cells in the absence of serum and HGFs enhanced the clonal growth of the cells in synergy with SDF-1. In contrast, IFN-gamma inhibited the clonal growth of hematopoietic progenitor cells in a standard methylcellulose clonogenic assay and inhibited the HGF-mediated survival of normal CD34+ cells. The addition of SDF-1 did not alter these outcomes. IFN-gamma did not enhance SDF-1-induced activation of PI3K/Akt or up-regulate the expression of CXCR4 or its function in bone marrow CD34+ cells. IFN-gamma up-regulated Socs1 messenger RNA expression in normal CD34+ cells, which was further enhanced with the addition of HGFs. These results indicate that IFN-gamma, partly in concert with SDF-1, exerts dual effects on the survival and growth of hematopoietic progenitor cells; the effects of IFN-gamma on hematopoietic progenitor cells can differ, depending on the particular in vitro experimental conditions, especially the presence of HGFs.
Hwang
Jin-Hee
JH
Division of Hematology/Oncology, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejon, Korea.
Kim
Seong-Woo
SW
Lee
Hyo-Jin
HJ
Yun
Hwan-Jung
HJ
Kim
Samyong
S
Jo
Deog-Yeon
DY
D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism* / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology
D018952:Antigens, CD34; D000970:Antineoplastic Agents; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D007371:Interferon-gamma