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Interleukin‐1β suppresses apoptosis in CD34 positive bone marrow cells through activation of the type I IL‐1 receptor
Author(s) -
Rodriguez C.,
Lacasse C.,
Hoang T.
Publication year - 1996
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199602)166:2<387::aid-jcp17>3.0.co;2-8
Subject(s) - cd34 , bone marrow , receptor , cytokine , neutralizing antibody , microbiology and biotechnology , biology , interleukin 3 , cell culture , antibody , interleukin 15 , interleukin , t cell , chemistry , il 2 receptor , immunology , immune system , stem cell , biochemistry , genetics
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‐1β 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‐1β 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‐1β 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‐1β results in a transient accumulation of GM‐CSF mRNA, with a peak at 3 h, which was dramatically decreased by neutralizing anti‐IL‐1RI 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‐1β 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‐1β in TF‐1 cells. © 1996 Wiley‐Liss, Inc.