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Apoptosis

Induction of apoptosis in human hematopoietic U937 cells by granulocyte–macrophage colony-stimulating factor: possible existence of caspase 3-like pathway

Leukemia volume 14, pages 612–619 (2000)Cite this article

Abstract

Granulocyte–macrophage colony-stimulating factor (GM-CSF) induced apoptosis in human hematopoietic U937 cells by itself and in a synergistic manner with tumor necrosis factor (TNF). GM-CSF-induced apoptosis was not inhibited by caspase inhibitors YVAD-CMK, DEVD-CHO and z-VAD-FMK, under the condition that these inhibitors potently suppressed TNF-induced apoptosis. Both GM-CSF and TNF induced caspase 3-like activity in this cell line though the time course was distinct between two cytokines, and combined stimulation of cells with GM-CSF plus TNF induced additive or synergistic activation of caspase 3-like activity. Amount of immunoreactive cleaved forms of caspase 3 recognized by specific antibody was completely dissociated with its enzymatic activity when the cells were stimulated with GM-CSF, but not with TNF. These results indicate that GM-CSF induces apoptosis of U937 cells via unknown pathway, which seems to be mediated by caspase 3-like activity, yet not caspase 3 itself, resistant to the caspase inhibitors, and synergistically interacts with conventional caspase 3 pathway of TNF. Possible involvement of caspases 1 and 8 (-like activity) but not caspase 7 in this pathway was also suggested.

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Acknowledgements

The authors would like to thank Dr Seiichi Kitagawa for providing human hematopoietic cell lines. This work was supported in part by a Grant-in-Aid for the Second Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan.

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Authors and Affiliations

  1. Department of Hematology, Research Institute, International Medical Center of Japan, Tokyo, Japan

    E Okuma, K Saeki, E Yasugi & A Yuo

  2. Department of Intractable Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan

    M Shimura & Y Ishizaka

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  1. E Okuma
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Okuma, E., Saeki, K., Shimura, M. et al. Induction of apoptosis in human hematopoietic U937 cells by granulocyte–macrophage colony-stimulating factor: possible existence of caspase 3-like pathway. Leukemia 14, 612–619 (2000). https://doi.org/10.1038/sj.leu.2401716

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