Exposure of foetal neural progenitor cells to IL-1β impairs their proliferation and alters their differentiation - a role for maternal inflammation?

J Neurochem. 2012 Mar;120(6):964-73. doi: 10.1111/j.1471-4159.2011.07634.x. Epub 2012 Feb 9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Embryo, Mammalian
  • Gene Expression Regulation, Developmental / drug effects
  • Interleukin-18 Receptor alpha Subunit / genetics
  • Interleukin-18 Receptor alpha Subunit / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology*
  • Mesencephalon / cytology*
  • Mesencephalon / embryology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-1 / metabolism
  • Signal Transduction / drug effects
  • Tetrazolium Salts
  • Thiazoles
  • Time Factors


  • Interleukin-18 Receptor alpha Subunit
  • Interleukin-1beta
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, Interleukin-1
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue