title: 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.
authors.affiliation: EA 4369, Université de Lorraine, Nancy, France.
authors.forename: Nader
authors.initials: N
authors.lastname: Hadife
authors.forename: Christophe
authors.initials: C
authors.lastname: Nemos
authors.forename: Jean-Pol
authors.initials: JP
authors.lastname: Frippiat
authors.forename: Tala
authors.initials: T
authors.lastname: Hamadé
authors.forename: Aurore
authors.initials: A
authors.lastname: Perrot
authors.forename: Ali
authors.initials: A
authors.lastname: Dalloul
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D000099180:Interleukin-24
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D053181:Caspase 8; D003576:Electron Transport Complex IV; D007334:Insulin-Like Growth Factor I; D007378:Interleukins; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D000099180:Interleukin-24; C494814:BID protein, human; C404795:COX6c protein, human; C496843:COX7B protein, human; C505530:CASP8 protein, human