Regulation of M-CSF production by cultured human thymic epithelial cells

We have studied the regulation of M-CSF production by human thymic epithelial cells (TEC) in a continuing effort to better understand the contribution of TEC to the intrathymic cytokine network. The levels of M-CSF were measured by radioimmunoassay. Five different TEC cultures were studied and we found that all cells examined produced M-CSF constitutively. We also studied the effects of cytokines on the regulation of the M-CSF secretion profile. IL-1, which strongly induces the secretion of a number of cytokines in TEC, was found to up-regulate M-CSF levels. The effects of IL-1 were dose and time dependent suggesting a direct effect on TEC. IFN-gamma is known to up-regulate cell surface antigens, and to modulate the IL-1-induced cytokine response in TEC. IFN-gamma could induce M-CSF by itself, but the effects were less pronounced than those of IL-1. IFN-gamma did not modify the IL-1-induced M-CSF. IL-4, which has been shown to partially modulate the IL-1-induced GM-CSF in TEC, had no effect on constitutive or induced M-CSF levels. These data are discussed in the context of the regulation of myelopoietic growth factor production by thymic stromal cells.