During pregnancy, activation of the maternal immune system
results in inflammation in the foetal nervous system. The causative agents are
pro-inflammatory cytokines like interleukin-1β (IL-1β), produced by the foetus.
In this study, we examine the effect of IL-1β on the proliferation and
differentiation of neural progenitor cells (NPCs) to better understand its
potential effects on the developing brain. We find that the IL-1β receptor
(IL-1R1) is expressed in the ventral mesencephalon of the developing brain.
Furthermore, IL-1R1 is expressed on Nestin-positive, Sox-2-positive NPCs. IL-1β
treatment reduced the numbers of proliferating NPCs, an effect prevented by the
IL-1R1 receptor antagonist. LDH and MTT assays, and western blot analysis for
cleaved caspase 3 and poly(ADP-ribose) polymerase, confirmed that this was not
due to an increase in cell death but rather an induction of differentiation. To
further study the effects of IL-1β on cell fate determination, we differentiated
NPCs in the presence and absence of IL-1β. Il-1β promoted gliogenesis and
inhibited neurogenesis, an effect that required p38-MAPK kinase signalling. In
summary, these data show that exposure of NPCs to IL-1β affects their
development. This necessitates an examination of the consequences that maternal
immune system activation during pregnancy has on the cellular architecture of
the developing brain.