Interferon-gamma inhibits apoptosis induced by wild-type p53, cytotoxic anti-cancer agents and viability factor deprivation in myeloid cells.
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.
Lotem
J
J
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
Sachs
L
L
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D005720:Gamma Rays; D015870:Gene Expression / Q000187:drug effects; D016158:Genes, p53; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007370:Interferon Type I; D015850:Interleukin-6; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D007371:Interferon-gamma