Interleukin-1β suppresses apoptosis in CD34 positive bone marrow cells through activation of the type I IL-1 receptor
✍ Scribed by C. Rodriguez; C. Lacasse; T. Hoang
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 596 KB
- Volume
- 166
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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-l p in the shortterm 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-lp are mediated by activation of type I IL-1 receptors (IL-1 RI) and induction of CM-CSF production. First, neutralizing antibodies to 11-1 RI but not IL-1 RII drastically abrogated cell survival induced by IL-1 p in CD34+/Lin-cells and TF-1 cells. Second, neutralizing antibodies against CM-CSF abrogate cell survival supported by IL-1 both in CD34+/Lin-bone marrow cells and in the cell line TF-l. Furthermore, exposure of TF-1 cells to IL-l p results in a transient accumulation of GM-CSF mRNA, with a peak at 3 h, which was dramatically decreased by neutralizing anti-IL-1 RI antibodies. In contrast, neutralizing anti-IL-lRII 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 p occurs through binding to IL-1 RI and the subsequent production of endogenous GM-CSF. IL-1 RII does not appear to be involved in signal transduction in primary CD34+/Lincells but could negatively regulate the response to IL-1 p in TF-1 cells.