Uric Acid Induces Trophoblast IL-1β Production Via the Inflammasome: Implications for the Pathogenesis of Preeclampsia

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

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)542-548
Number of pages7
JournalAmerican Journal of Reproductive Immunology
Volume65
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

Keywords

  • Inflammasome
  • Nod-like receptor
  • Placenta
  • Preeclampsia
  • Trophoblast
  • Uric acid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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