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Sallmon, H; Hoene, V; Weber, SC; Dame, C.
Differentiation of human SH-SY5Y neuroblastoma cells by all-trans retinoic acid activates the interleukin-18 system.
J Interferon Cytokine Res. 2010; 30(2):55-8
Doi: 10.1089/jir.2009.0036
Web of Science
PubMed
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- Leading authors Med Uni Graz
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Sallmon Hannes
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- Abstract:
- The clinical prognosis of children with high-stage neuroblastoma is still poor. Therapeutic approaches include surgery and cellular differentiation by retinoic acid, but also experimental interleukin-based immune modulation. However, the molecular mechanisms of all-trans retinoic acid (ATRA)-induced differentiation of neuroblastoma cells are incompletely understood. Herein, we examined the effect of ATRA on the activity of the interleukin-18 (IL-18) system in human SH-SY5Y neuroblastoma cells. It is shown that SH-SY5Y cells express IL-18 receptor (IL-18R) and the secreted antagonist IL-18-binding protein (IL-18BP), but no IL-18. SH-SY5Y cells are highly sensitive to ATRA treatment and react by cellular differentiation from a neuroblastic toward a more neuronal phenotype. This was associated with induction of IL-18 and reduction of IL-18BP expression, while IL-18R expression remained stable. Thereby, we identified the IL-18 system as a novel target of ATRA in neuroblastoma cells that might contribute to the therapeutic properties of retinoids in treatment of neuroblastoma.
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Cell Differentiation - drug effects
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Cell Line, Tumor - administration & dosage
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Humans - administration & dosage
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Intercellular Signaling Peptides and Proteins - metabolism
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Interleukin-18 - immunology
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Neuroblastoma - immunology, pathology
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Receptors, Interleukin-18 - biosynthesis
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Tretinoin - pharmacology