Interferon-gamma inhibits apoptosis induced by wild-type p53, cytotoxic anti-cancer agents and viability factor deprivation in myeloid cells

Abstract

Different hematopoietic cytokines including colony-stimulating factors and interleukins can inhibit apoptotic cell death induced in myeloid cells by the tumor-suppressor gene wild-type 53 and a variety of cytotoxic anti-cancer agents. In this study we identity interferon-gamma as an anti-apoptotic cytokine for myeloid cells in which apoptosis was induced by wild-type p53, cytotoxic anti-cancer agents or viability factor deprivation. The inhibition of wild-type p53-mediated apoptosis in myeloid leukemic cells by interferon-gamma was not associated with downregulated expression of wild-type p53 or the p53-induced cyclin-dependent kinase inhibitor gene WAF-1, or with upregulated expression of the apoptosis-inhibiting gene bcl-2. Interferon-gamma also inhibited induction of apoptosis by a p53-independent pathway. Interferon-gamma inhibited apoptotic cell death caused by withdrawal of viability factors in normal myeloid precursor cells, the interleukin 3-dependent 32D cell line and differentiating myeloid leukemic cells. Interferon-alpha/beta did not inhibit apoptotic cell death in any of these systems. The results indicate that although interferon-gamma can inhibit cell multiplication and differentiation in myeloid cells, it shares with other hematopoietic cytokines the ability to protect normal and leukemic myeloid cells from induction of apoptosis.