Phenotype dependent differential effects of interleukin-1β and amyloid-β on viability and cholinergic phenotype of T17 neuroblastoma cells

Amyloid-β accumulation in brains of Alzheimer's disease (AD) victims is accompanied by glial inflammatory reactions and preferential loss of cholinergic neurons. Therefore, the aim of this study was to find out whether proinflamatory cytokine interleukin 1β (IL1β) modifies effects of amyloid-β (Aβ) on viability and cholinergic phenotype of septum derived T17 cholinergic neuroblastoma cells. In nondifferentiated T17 cells (NC) Aβ(25-35) (1 μg/ml) caused no changes in choline acetyltransferase (ChAT) activity, acetylcholine (ACh) release, subcellular distribution of acetyl-CoA, but doubled content of trypan blue positive cells. IL1β (10 ng/ml) increased ACh release (125%) but did not change other parameters of NC. In the presence of Aβ IL1β also increased ChAT activity (47%), ACh release (100%) but had no effect on acetyl-CoA distribution and cell viability. Differentiation with retinoic acid and dibutyryl cyclic AMP caused over two-fold increase of ChAT activity and ACh content, four-fold increase of ACh release and about 50% decrease of acetyl-CoA level in the mitochondria. In differentiated cells (DC), Aβ decreased ChAT activity (31%), ACh release (47%) and content of acetyl-CoA (80%) in cell cytoplasmic compartment, whereas IL1β elevated ChAT activity (54%) and ACh release (32%). IL1β totally reversed Aβ-evoked inhibition of ChAT activity and ACh release and restored control level of cytoplasmic acetyl-CoA but increased fraction of nonviable cells to 25%. Thus, IL1β could compensate Aβ-evoked cholinergic deficits through the restoration of adequate expression of ChAT and provision of acetyl-CoA to cytoplasmic compartment in cholinergic neurons that survive under such pathologic conditions. These data indicate that IL1β posses independent cholinotrophic and cholinotoxic activities that may modify Aβ effects on cholinergic neurons.