Differentiation of human SH-SY5Y neuroblastoma cells by all-trans retinoic acid activates the interleukin-18 system.
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.
Sallmon
Hannes
H
Department of Neonatology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Hoene
Victoria
V
Weber
Sven C
SC
Dame
Christof
C
D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020382:Interleukin-18 / Q000276:immunology*; D009447:Neuroblastoma / Q000276:immunology* / Q000473:pathology*; D053724:Receptors, Interleukin-18 / Q000096:biosynthesis*; D014212:Tretinoin / Q000494:pharmacology*
D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D053724:Receptors, Interleukin-18; C118370:interleukin-18 binding protein; D014212:Tretinoin