The dual regulatory role of interleukin 4 is mediated through a direct effect on the target cell.
The mechanisms responsible for regulating the growth and differentiation of pluripotent stem cells involve the complex interaction of a series of specific and nonspecific growth factors and signals. In this report, colony-stimulating factor (CSF)-dependent clonal cell lines, recombinant and/or purified CSFs, and clonal assays were used to investigate the mechanism of interleukin 4 (IL-4)-induced modulation of CSF-dependent cell growth. IL-4 inhibits in a dose-dependent fashion either the interleukin 3 (IL-3)- or granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced growth of the myelomonocytic progenitor cell line, FDC-P1. This inhibitory effect of IL-4- on IL-3- or GM-CSF-induced cell growth was verified using normal bone marrow cells. Our data supports the hypothesis that IL-4 is acting directly on the progenitor cell and not indirectly through the action of accessory cells. Further, because the inhibitory effect of IL-4 is selective and does not affect all CSF-dependent cell lines, other factors, including the maturational state or the lineage of the cell may be important in dictating an effect, if any, mediated by IL-4.
Searle Research and Development, Monsanto Company, St. Louis, Missouri.
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McKearn
D000818:Animals; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology; D051379:Mice
D007377:Interleukin-3; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor