Involvement of Cytokine IL-1Ra in Regulating the Secretion of VEGF in SH-SY5Y Neuroblastoma
Inflammation, neurodevelopment, and cancer are associated with cellular features of signal transduction using molecules originally identified with functions that are part of the extended immune system. The expression of interleukin-1 (IL-1) and interleukin-1 receptor antagonist (IL-1Ra) is currently not well understood in human neuronal cell types. The development of neutraceuticals from natural products as inexpensive preventative therapies to protect against neurodevelopment disorders, neurodegeneration and cancer is a current focus of biotechnology research. To further study the role of cytokines in early stage neuroinflammation, neurodegeneration and brain cancer, SH-SY5Y neuroblastoma cells were characterized for the presence of the IL-1 and IL1Ra, as well as vascular endothelial growth factor (VEGF). The expression of these cytokines was measured using sensitive ELISA assays before and after stressing the cells with TNF-. Using partially purified extract fractions of the wild Alaskan Bog Blueberries (BBX) on these cytokines and VEGF, the cells were pretreated with different BBX extract prior to TNF- exposure, and cytokine measurement. Intracellular IL- 1Ra levels increased (13.6 g/mL) after exposure to TNF- when compared to non-treated cells (6.7 g/mL). VEGF levels in the culture supernatant also increased compared to the control, 217.3 g/mL versus 172.2 g/mL, respectively. BBX 8 increased intracellular IL-1Ra protein levels (25.2 g/mL), while returning VEGF levels to normal. We hypothesize that compounds in blueberries enhance the signal transduction feedback leading to a restoration of the intracellular balance between IL-1 and IL-1Ra signals.