title: Exposure of foetal neural progenitor cells to IL-1β impairs their proliferation and alters their differentiation - a role for maternal inflammation?
abstract: 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.
authors.affiliation: Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Crampton
authors.forename: Louise M
authors.initials: LM
authors.lastname: Collins
authors.forename: Andre
authors.initials: A
authors.lastname: Toulouse
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Nolan
authors.forename: Gerard W
authors.initials: GW
authors.lastname: O'Keeffe
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053727:Interleukin-18 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology* / Q000196:embryology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
chemical_list: D053727:Interleukin-18 Receptor alpha Subunit; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue