Survival of the myeloid progenitor cell line FDC-P1 is prolonged by interferon-gamma or interleukin-4.
Continuous proliferation of the immortalized myeloid progenitor cell line FDC-P1 depends on stimulation with either interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF). Two other cytokines, interferon-gamma (IFN-gamma) and IL-4, were found to prolong FDC-P1 survival for several days. Surviving cells incorporated [3H]thymidine and a minority completed up to 3 cell divisions before dying. This transient proliferative response was a direct effect of IFN-gamma and IL-4 since these cytokines did not induce production of detectable IL-3 or GM-CSF and the response was unaffected by cell concentration. IL-6, a constitutive product of FDC-P1 cells whose secretion was increased by IL-3, GM-CSF and IL-4 but not by IFN-gamma, was not responsible for the proliferative response. FDC-P1 lines that constitutively expressed the cell cycle-associated oncogene myc or the survival-associated oncogene bcl-2 also responded only transiently to IFN-gamma or IL-4, indicating that expression of these genes did not complement the signals delivered by IFN-gamma or IL-4. By contrast, the protein kinase C activator phorbol 12-myristate 13-acetate (PMA) prolonged survival of FDC-P1 cells on its own and potentiated the response to IFN-gamma or IL-4, although the combination of stimuli did not support long-term growth. It is concluded that IFN-gamma and IL-4 trigger only some of the signalling events that lead to mitogenesis; these events are complemented by stimulation with PMA but additional signals are required for sustained proliferation.
Kelso
A
A
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
Troutt
A B
AB
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D016259:Genes, myc; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D009857:Oncogenes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D016207:Cytokines; D007377:Interleukin-3; D015847:Interleukin-4; D015759:Ionomycin; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate