Document Detail


TLR9 provokes inflammation in response to fetal DNA: mechanism for fetal loss in preterm birth and preeclampsia.
MedLine Citation:
PMID:  22544937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Preterm birth, the major cause of neonatal mortality in developed countries, is associated with intrauterine infections and inflammation, although the exact mechanisms underlying this event are unclear. In this study, we show that circulating fetal DNA, which is elevated in pregnancies complicated by preterm labor or preeclampsia, triggers an inflammatory reaction that results in spontaneous preterm birth. Fetal DNA activates NF-κB, shown by IκBα degradation in human PBMCs resulting in production of proinflammatory IL-6. We show that fetal resorption and preterm birth are rapidly induced in mice after i.p. injection of CpG or fetal DNA (300 μg/dam) on gestational day 10-14. In contrast, TLR9(-/-) mice were protected from these effects. Furthermore, this effect was blocked by oral administration of the TLR9 inhibitor chloroquine. Our data therefore provide a novel mechanism for preterm birth and preeclampsia, highlighting TLR9 as a potential therapeutic target for these common disorders of pregnancy.
Authors:
Andrea Scharfe-Nugent; Sinéad C Corr; Susan B Carpenter; Louise Keogh; Brendan Doyle; Cara Martin; Katherine A Fitzgerald; Sean Daly; John J O'Leary; Luke A J O'Neill
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-27
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  188     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-05-21     Completed Date:  2012-08-14     Revised Date:  2013-07-29    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5706-12     Citation Subset:  AIM; IM    
Affiliation:
Department of Obstetrics and Gynaecology, Coombe Women & Infants University Hospital, Dublin 8, Ireland.
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Cell Line, Tumor
Cells, Cultured
DNA / blood,  genetics*
Female
Fetal Death / genetics,  immunology*
Humans
Inflammation Mediators / adverse effects,  blood,  physiology*
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Pre-Eclampsia / epidemiology*
Pregnancy
Premature Birth / epidemiology*
Toll-Like Receptor 9 / biosynthesis,  deficiency,  physiology*
Chemical
Reg. No./Substance:
0/Inflammation Mediators; 0/Tlr9 protein, mouse; 0/Toll-Like Receptor 9; 9007-49-2/DNA
Comments/Corrections
Comment In:
J Immunol. 2013 Jun 15;190(12):5909   [PMID:  23749963 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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