Document Detail


Uric acid induces trophoblast IL-1β production via the inflammasome: implications for the pathogenesis of preeclampsia.
MedLine Citation:
PMID:  21352397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PROBLEM: Preeclampsia is associated with hyperuricemia, which correlates with the disease severity. Levels of circulating uric acid increase before the clinical manifestations, suggesting that they may be causally related. Uric acid, or monosodium urate (MSU), activates the Nod-like receptor, Nalp3, leading to inflammasome activation and IL-1β processing. Because preeclampsia is associated with placental immune⁄ inflammatory dysregulation, we sought to determine in the trophoblast, the presence of the Nalp3 inflammasome, and the effect of MSU on its activation.
METHOD OF STUDY: Isolated first- and third-trimester trophoblasts were assessed for expression of the inflammasome components, Nalp1, Nalp3, and ASC. First-trimester trophoblast cells were incubated with or without MSU, and after which, IL-1β secretion and processing and caspase-1 activation were determined.
RESULTS: Trophoblast cells expressed Nalp1, Nalp3, and ASC under basal conditions. Following incubation with MSU, first-trimester trophoblast IL-1β secretion was upregulated. This correlated with increased expression levels of active IL-1β and active caspase-1. ASC knockdown reduced MSU-induced IL-1β secretion.
CONCLUSION: These findings demonstrate that uric acid activates the inflammasome in the trophoblast, leading to IL-1β production. This may provide a novel mechanism for the induction of inflammation at the maternal–fetal interface leading to placental dysfunction and adverse pregnancy outcome, including preeclampsia.
Authors:
Melissa J Mulla; Kledia Myrtolli; Julie Potter; Crina Boeras; Paula B Kavathas; Anna K Sfakianaki; Serkelem Tadesse; Errol R Norwitz; Seth Guller; Vikki M Abrahams
Related Documents :
18967267 - Spectrophotometric determination of nitrite based on its catalytic effect on the oxidat...
3227307 - Olsalazine-o-sulphate: an acid labile metabolite of olsalazine.
7447367 - A discrete multichannel procedure for the determination of acid phosphatase activities ...
11393207 - Corticosteroid-induced atrophy and barrier impairment measured by non-invasive methods ...
2347397 - The effect of endotoxin on membrane fatty acid composition in bcg-sensitized mice.
10448517 - Regulation of gene expression by dietary fat.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of reproductive immunology (New York, N.Y. : 1989)     Volume:  65     ISSN:  1600-0897     ISO Abbreviation:  Am. J. Reprod. Immunol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-10     Completed Date:  2011-08-29     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8912860     Medline TA:  Am J Reprod Immunol     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  542-8     Citation Subset:  IM    
Affiliation:
Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University, New Haven, CT 06510, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / immunology,  metabolism
Apoptosis Regulatory Proteins / immunology,  metabolism
Carrier Proteins / immunology,  metabolism
Caspase 1 / immunology,  metabolism
Cell Line
Cytoskeletal Proteins / immunology,  metabolism
Disease Progression
Enzyme Activation / drug effects
Female
Gene Expression Regulation, Developmental / drug effects
Humans
Hyperuricemia
Inflammasomes / drug effects*,  immunology,  metabolism
Interleukin-1beta / metabolism*
Maternal-Fetal Relations
Pre-Eclampsia / blood,  immunology*,  physiopathology
Pregnancy
Trophoblasts / drug effects*,  metabolism,  pathology
Uric Acid / blood,  pharmacology*
Grant Support
ID/Acronym/Agency:
R01 AI049571-05/AI/NIAID NIH HHS; R01049571//PHS HHS
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Apoptosis Regulatory Proteins; 0/Carrier Proteins; 0/Cytoskeletal Proteins; 0/Inflammasomes; 0/Interleukin-1beta; 0/NLRP1 protein, human; 0/NLRP3 protein, human; 0/PYCARD protein, human; 69-93-2/Uric Acid; EC 3.4.22.36/Caspase 1
Comments/Corrections

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


Previous Document:  Rescue and worsening of congenital heart block-associated electrocardiographic abnormalities in two ...
Next Document:  Preliminary Investigation of the Panic Screening Score for Emergency Department Patients With Unexpl...