Interferon-γ attenuates the survival activity of G-CSF through PI3K/Akt signaling pathway in mouse multipotent progenitor cells

Hong Liu, Keichiro Mihara, Guoqi Song, Hideo Tanaka, Akiro Kimura

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)547-555
Number of pages9
JournalAnnals of Hematology
Volume86
Issue number8
DOIs
Publication statusPublished - 01-08-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Hematology

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