Involvement of Cytokine IL-1Ra in Regulating the Secretion of VEGF in SH-SY5Y Neuroblastoma

Abstract

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.