Different IL-1β levels differentially mediate neuroprotection or neurodegeneration and may be related to BDNF

The detrimental and protective effects of interleukin 1β (IL-1β) have been reported. We have previously shown that the periods of IL-1β elevation is related to its dual effects. However, the effects of different IL-1β concentrations on neuropathological processes are unclear. Studies have demonstrated that mature brain-derived neurotrophic factor (mBDNF) and its precursor (proBDNF) have opposing functions in neuronal survival. We previously showed that mBDNF is involved in IL-1β-mediated neuropathology. Here, we investigated whether different IL-1β concentrations differentially affect mBDNF and proBDNF, determining their beneficial or harmful effects.

HT22 cells were cultured and exposed to various IL-1β concentrations for different durations. HT22 cell viability and the expression of mBDNF, proBDNF and their receptors were evaluated by a Cell Counting Kit-8 (CCK-8) assay and western blot.

Compared with untreated cells, a significant reduction in cell viability was observed after exposure to high IL-1β concentrations for more than 24 h. Increased expression of proBDNF and its receptor p75NTR and decreased expression of mBDNF and its receptor TrkB, as well as decreased furin and PC1/3 (which promote the cleavage of proBDNF to mBDNF) expression, were detected. In contrast, low IL-1β concentrations increased cell viability, but a significant effect was observed only at an optimal concentration; in contrast to our predictions, low IL-1β concentrations did not induce significant alterations in mBDNF and proBDNF expression levels, but rather, low concentrations significantly increased the mBDNF/proBDNF ratio.

These results demonstrated that changes induced by low (neuroprotection) and high (neurodegeneration) IL-1β concentrations were oriented in different directions. These dual effects occur partly through the modulation of mBDNF signaling.