Abstract
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 fol...Continue Reading
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