Present address: Department of Obstetrics & Gynecology, Tufts Medical Center, Boston, MA, USA.
Uric Acid Induces Trophoblast IL-1β Production Via the Inflammasome: Implications for the Pathogenesis of Preeclampsia
Article first published online: 18 JAN 2011
© 2011 John Wiley & Sons A/S
American Journal of Reproductive Immunology
Volume 65, Issue 6, pages 542–548, June 2011
How to Cite
Mulla, M. J., Myrtolli, K., Potter, J., Boeras, C., Kavathas, P. B., Sfakianaki, A. K., Tadesse, S., Norwitz, E. R., Guller, S. and Abrahams, V. M. (2011), Uric Acid Induces Trophoblast IL-1β Production Via the Inflammasome: Implications for the Pathogenesis of Preeclampsia. American Journal of Reproductive Immunology, 65: 542–548. doi: 10.1111/j.1600-0897.2010.00960.x
- Issue published online: 25 APR 2011
- Article first published online: 18 JAN 2011
- Submitted November 19, 2010; accepted November 29, 2010.
- Nod-like receptor;
- uric acid
Citation Mulla MJ, Myrtolli K, Potter J, Boeras C, Kavathas PB, Sfakianaki AK, Tadesse S, Norwitz ER, Guller S, Abrahams VM. Uric acid induces trophoblast IL-1β production via the inflammasome: implications for the pathogenesis of preeclampsia. Am J Reprod Immunol 2010; 65: 542–548
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.