Document Detail


Toll-like receptor 9 activation: a novel mechanism linking placenta-derived mitochondrial DNA and vascular dysfunction in pre-eclampsia.
MedLine Citation:
PMID:  22671429     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Emerging evidence suggests that in addition to being the 'power houses' of our cells, mitochondria facilitate effector responses of the immune system. Cell death and injury result in the release of mtDNA (mitochondrial DNA) that acts via TLR9 (Toll-like receptor 9), a pattern recognition receptor of the immune system which detects bacterial and viral DNA but not vertebrate DNA. The ability of mtDNA to activate TLR9 in a similar fashion to bacterial DNA stems from evolutionarily conserved similarities between bacteria and mitochondria. mtDNA may be the trigger of systemic inflammation in pathologies associated with abnormal cell death. PE (pre-eclampsia) is a hypertensive disorder of pregnancy with devastating maternal and fetal consequences. The aetiology of PE is unknown and removal of the placenta is the only effective cure. Placentas from women with PE show exaggerated necrosis of trophoblast cells, and circulating levels of mtDNA are higher in pregnancies with PE. Accordingly, we propose the hypothesis that exaggerated necrosis of trophoblast cells results in the release of mtDNA, which stimulates TLR9 to mount an immune response and to produce systemic maternal inflammation and vascular dysfunction that lead to hypertension and IUGR (intra-uterine growth restriction). The proposed hypothesis implicates mtDNA in the development of PE via activation of the immune system and may have important preventative and therapeutic implications, because circulating mtDNA may be potential markers of early detection of PE, and anti-TLR9 treatments may be promising in the management of the disease.
Authors:
Styliani Goulopoulou; Takayuki Matsumoto; Gisele F Bomfim; R Clinton Webb
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  123     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-06-07     Completed Date:  2012-08-14     Revised Date:  2014-05-11    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  429-35     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA, Mitochondrial / physiology*
Female
Fetal Growth Retardation / immunology,  physiopathology,  therapy
Humans
Hypertension, Pregnancy-Induced / immunology,  physiopathology*,  therapy
Inflammation / immunology,  physiopathology,  therapy
Placenta / pathology,  physiology*
Pre-Eclampsia / immunology,  physiopathology*,  therapy
Pregnancy
Signal Transduction / physiology
Toll-Like Receptor 9 / antagonists & inhibitors,  physiology*
Grant Support
ID/Acronym/Agency:
R01 DK083685/DK/NIDDK NIH HHS; R01 DK083685/DK/NIDDK NIH HHS; R01 HL071138/HL/NHLBI NIH HHS; R01 HL071138/HL/NHLBI NIH HHS; T32 HL066993/HL/NHLBI NIH HHS; T32 HL066993-09/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Mitochondrial; 0/TLR9 protein, human; 0/Toll-Like Receptor 9
Comments/Corrections

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