Interleukin-1 beta suppresses apoptosis in CD34 positive bone marrow cells through activation of the type I IL-1 receptor.
Interleukin-1 is a pleiotropic cytokine that has been shown previously to suppress active cell death in T cells. Two cell surface receptors for interleukin-1 have been identified and their genes cloned, type I (IL-RI) and type II (IL-RII) receptors. In the present study, we provide evidence for a role of interleukin-1 beta in the short-term suppression of cell death both in purified CD34+/Lin- bone marrow precursors and in the GM-CSF dependent cell line TF-1. Several lines of evidence suggest that the biologic effects of IL-1 beta are mediated by activation of type I IL-1 receptors (IL-1RI) and induction of GM-CSF production. First, neutralizing antibodies to IL-1RI but not IL-1RII drastically abrogated cell survival induced by IL-1 beta in CD34+/Lin- cells and TF-1 cells. Second, neutralizing antibodies against GM-CSF abrogate cell survival supported by IL-1 both in CD34+/Lin- bone marrow cells and in the cell line TF-1. Furthermore, exposure of TF-1 cells to IL-1 beta results in a transient accumulation of GM-CSF mRNA, with a peak at 3 h, which was dramatically decreased by neutralizing anti-IL-1R1 antibodies. In contrast, neutralizing anti-IL-1RII did not change the IL-1 induced cell survival of bone marrow cells and was followed by a paradoxical increase in viable cell numbers, in c-myc and c-myb mRNA accumulation in IL-1 treated TF-1 cells. Together our results indicate that the increase in cell survival induced IL-1 beta occurs through binding to IL-1RI and the subsequent production of endogenous GM-CSF. IL-1RII does not appear to be involved in signal transduction in primary CD34+/Lin- cells but could negatively regulate the response to IL-1 beta in TF-1 cells.
Rodriguez
C
C
Clinical Research Institute of Montreal, University of Montreal, Québec, Canada.
Lacasse
C
C
Hoang
T
T
D018952:Antigens, CD34 / Q000032:analysis*; D017209:Apoptosis; D001853:Bone Marrow / Q000502:physiology; D001854:Bone Marrow Cells; D002470:Cell Survival; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor