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Activation of the maternal immune system induces endocrine changes in the placenta via IL-6

Hsiao, Elaine Y. and Patterson, Paul H. (2011) Activation of the maternal immune system induces endocrine changes in the placenta via IL-6. Brain, Behavior, and Immunity, 25 (4). pp. 604-615. ISSN 0889-1591. PMCID PMC3081363. doi:10.1016/j.bbi.2010.12.017.

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Activation of the maternal immune system in rodent models sets in motion a cascade of molecular pathways that ultimately result in autism- and schizophrenia-related behaviors in offspring. The finding that interleukin-6 (IL-6) is a crucial mediator of these effects led us to examine the mechanism by which this cytokine influences fetal development in vivo. Here we focus on the placenta as the site of direct interaction between mother and fetus and as a principal modulator of fetal development. We find that maternal immune activation (MIA) with a viral mimic, synthetic double-stranded RNA (poly(I:C)), increases IL-6 mRNA as well as maternally-derived IL-6 protein in the placenta. Placentas from MIA mothers exhibit increases in CD69+ decidual macrophages, granulocytes and uterine NK cells, indicating elevated early immune activation. Maternally-derived IL-6 mediates activation of the JAK/STAT3 pathway specifically in the spongiotrophoblast layer of the placenta, which results in expression of acute phase genes. Importantly, this parallels an IL-6-dependent disruption of the growth hormone-insulin-like growth factor (GH-IGF) axis that is characterized by decreased GH, IGFI and IGFBP3 levels. In addition, we observe an IL-6-dependent induction in pro-lactin-like protein-K (PLP-K) expression as well as MIA-related alterations in other placental endocrine factors. Together, these IL-6-mediated effects of MIA on the placenta represent an indirect mechanism by which MIA can alter fetal development.

Item Type:Article
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URLURL TypeDescription CentralArticle
Hsiao, Elaine Y.0000-0002-1633-588X
Additional Information:© 2010 Elsevier Inc. Received 22 November 2010; Received in revised form 21 December 2010; Accepted 22 December 2010; Available online 30 December 2010. The authors acknowledge the kind assistance of B. Deverman and A. Bonnin with reviewing the manuscript; A. Colon, L. Sandoval and R. Sauza with caring for and maintaining the animals; and N. Tetreault and D. Anderson with providing the LMD and qPCR equipment. This research was supported by an Autism Speaks Dennis Weatherstone Pre-Doctoral Fellowship and by a Caltech training grant from the National Institutes of Health (NIH/NRSA 5 T32 GM07737).
Funding AgencyGrant Number
NIH Predoctoral Fellowship5 T32 GM07737
Subject Keywords:Autism; Schizophrenia; Maternal immune activation; Inflammation; Growth hormone; Insulin-like growth factor; JAK/STAT3; Poly(I:C); Maternal infection
Issue or Number:4
PubMed Central ID:PMC3081363
Record Number:CaltechAUTHORS:20110531-100559236
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Official Citation:Elaine Y. Hsiao, Paul H. Patterson, Activation of the maternal immune system induces endocrine changes in the placenta via IL-6, Brain, Behavior, and Immunity, Volume 25, Issue 4, May 2011, Pages 604-615, ISSN 0889-1591, DOI: 10.1016/j.bbi.2010.12.017.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:23833
Deposited On:31 May 2011 21:22
Last Modified:09 Nov 2021 16:18

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