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

Autor: Nader Hadife, Tala Hamadé, Aurore Perrot, Christophe Nemos, Jean-Pol Frippiat, Ali Dalloul
Přispěvatelé: Relations Hôte-Environnement ( RHEM ), Université Henri Poincaré - Nancy 1 ( UHP ), Déficiences Mentales et Anomalies de Structure du Génome ( DMASG ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Développement et Immunogénétique ( LDI ), Stress, Immunité, Pathogènes ( SIMPA ), Université de Lorraine ( UL ), Faculté de Médecine [Nancy], Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Relations Hôte-Environnement (RHEM), Université Henri Poincaré - Nancy 1 (UHP), Déficiences Mentales et Anomalies de Structure du Génome (DMASG), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Développement et Immunogénétique (LDI), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Cancer Research
Time Factors
medicine.medical_treatment
Transactivation
0302 clinical medicine
[ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology
IL-24
Interleukin 24
Tumor Cells
Cultured
[ SDV.IMM ] Life Sciences [q-bio]/Immunology
Insulin-Like Growth Factor I
Child
Cells
Cultured
Oligonucleotide Array Sequence Analysis
bcl-2-Associated X Protein
Inhibitor of apoptosis domain
0303 health sciences
B-Lymphocytes
Caspase 8
Reverse Transcriptase Polymerase Chain Reaction
apoptosis
Interleukin
Hematology
Recombinant Proteins
3. Good health
Cell biology
Mitochondria
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Oncology
030220 oncology & carcinogenesis
Child
Preschool
[SDV.IMM]Life Sciences [q-bio]/Immunology
BH3 Interacting Domain Death Agonist Protein
Signal Transduction
Programmed cell death
Blotting
Western
B-cells
gene arrays
Biology
Electron Transport Complex IV
03 medical and health sciences
medicine
Humans
030304 developmental biology
Cell growth
Growth factor
Interleukins
Cell Cycle Checkpoints
Leukemia
Lymphocytic
Chronic
B-Cell
Apoptosis
Cancer research
Tumor Suppressor Protein p53
Transcriptome
Zdroj: Leukemia & lymphoma
Leukemia & lymphoma, Taylor & Francis, 2013, 54 (3), pp.587-597. 〈http://www.tandfonline.com/doi/abs/10.3109/10428194.2012.717079?journalCode=ilal20〉. 〈10.3109/10428194.2012.717079〉
Leukemia & lymphoma, Taylor & Francis, 2013, 54 (3), pp.587-597. ⟨10.3109/10428194.2012.717079⟩
ISSN: 1042-8194
1029-2403
DOI: 10.3109/10428194.2012.717079?journalCode=ilal20〉.
Popis: International audience; 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.
Databáze: OpenAIRE
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