caa a22 4500 46325645X CHVBK 20180405153357.0 cr unu---uuuuu 170326e20070801xx s 000 0 eng 10.1007/s00277-007-0308-4 doi (NATIONALLICENCE)springer-10.1007/s00277-007-0308-4 Interferon-γ attenuates the survival activity of G-CSF through PI3K/Akt signaling pathway in mouse multipotent progenitor cells [Elektronische Daten] [Hong Liu, Keichiro Mihara, Guoqi Song, Hideo Tanaka, Akiro Kimura] Apoptosis plays an important role in the injury to stem and progenitor compartments associated with aberrant interferon-gamma (IFN-γ) in aplastic anemia (AA), which is characterized by the loss of stem cells; however, its molecular mechanism is poorly understood. In this study, we have addressed the mechanism of the apoptotic function of IFN-γ against hematopoietic stem and/or progenitors. Although granulocyte colony-stimulating factor (G-CSF) augmented survival and proliferative and differentiating activity in 32D cells, mouse multipotent progenitor cells, these effects were abolished by IFN-γ and were susceptible to apoptosis with IFN-γ. IFN-γ attenuated Akt phosphorylated by G-CSF in a dose- and time-dependent manner. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), enhanced the inhibitory effect on Akt phosphorylated by G-CSF in collaboration with IFN-γ, suggesting that the activity of IFN-γ might converge on the PI3K pathway. We examined the expression of Bcl-2-associated death (Bad), which works downstream of Akt. IFN-γ increased the Bad protein reduced by G-CSF. IFN-γ induced apoptosis in 32D cells through the caspase pathway. Taken together, these results suggest that IFN-γ could exert inhibitory action on stem cells and/or progenitors by interference with the PI3K/Akt signaling pathway. Our findings may contribute to understanding the decreased number of stem cells characteristic of AA. Springer-Verlag, 2007 Interferon-γ nationallicence Akt nationallicence Phosphatidylinositol 3-kinase nationallicence Progenitor cells nationallicence G-CSF nationallicence Liu Hong Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan aut Mihara Keichiro Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan aut Song Guoqi Department of Hematology, Hospital of Nantong University, Nantong, Jiangsu, China aut Tanaka Hideo Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan aut Kimura Akiro Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan aut Annals of Hematology Springer-Verlag 86/8(2007-08-01), 547-555 0939-5555 86:8<547 2007 86 277 https://doi.org/10.1007/s00277-007-0308-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00277-007-0308-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liu Hong Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan aut NATIONALLICENCE 700 1- Mihara Keichiro Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan aut NATIONALLICENCE 700 1- Song Guoqi Department of Hematology, Hospital of Nantong University, Nantong, Jiangsu, China aut NATIONALLICENCE 700 1- Tanaka Hideo Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan aut NATIONALLICENCE 700 1- Kimura Akiro Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, 734-8553, Hiroshima, Japan aut NATIONALLICENCE 773 0- Annals of Hematology Springer-Verlag 86/8(2007-08-01), 547-555 0939-5555 86:8<547 2007 86 277 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer