Interleukin-24 mediates apoptosis in human B-cells through early activation of cell cycle arrest followed by late induction of the mitochondrial apoptosis pathway - Université de Lorraine Access content directly
Journal Articles Leukemia & lymphoma Year : 2013

Interleukin-24 mediates apoptosis in human B-cells through early activation of cell cycle arrest followed by late induction of the mitochondrial apoptosis pathway

Abstract

Interleukin (IL)-24 has death-promoting effects on various proliferating cells including B-cells from chronic lymphocytic leukemia (CLL) and germinal center B-cells, but its molecular mechanisms are poorly understood. Using a B-cell differentiation model and mRNA profiling, we found that recombinant (r)IL-24 stimulated genes of the mitochondrial apoptotic pathway (Bax, Bid, Casp8, COX6C, COX7B) after 36 h, whereas the transcription of genes involved in DNA replication and metabolism was inhibited within 6 h. Unexpectedly, insulin-like growth factor 1 (IGF1), a hormone known to promote cell growth, was stimulated by IL-24. Activated B-cells express receptor for IGF1, to which they become sensitized and undergo apoptosis, a mechanism similar in this respect to IL-24-induced cell death. Furthermore, inhibition of the IGF1 pathway reversed the effects of IL-24. IL-24-mediated apoptosis was also antagonized by pifithrin-alpha, an inhibitor of p53 transactivation. Altogether, these results disclose sequential molecular signals generated by IL-24 in activated B-cells.
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hal-01480513 , version 1 (01-03-2017)

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Nader Hadife, Christophe Nemos, Jean-Pol Frippiat, Tala Hamadé, Aurore Perrot, et al.. Interleukin-24 mediates apoptosis in human B-cells through early activation of cell cycle arrest followed by late induction of the mitochondrial apoptosis pathway. Leukemia & lymphoma, 2013, 54 (3), pp.587-597. ⟨10.3109/10428194.2012.717079⟩. ⟨hal-01480513⟩
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