Abstract
Introduction Preeclampsia (PE) is a pregnancy disorder characterized by an imbalance between pro- and anti-inflammatory cytokines associated with high plasma levels of uric acid and Interleukin-1 beta (IL-1 β ) in the severe cases of PE. Uric acid acts as a danger-associated molecular pattern (DAMP) and activates the inflammasome in the trophoblast cells, leading to IL-1 β secretion. Inflammasomes are intracellular multiprotein complexes which mediate innate immune response via caspase-1 activation, resulting in IL-1 β and IL-18 secretion in their active forms. Objectives As placenta seems to play an important role in the pathogenesis of PE the present study aimed to investigate the expression of gene and proteins related to the inflammasome in placenta from preeclamptic women. Methods Placental tissue was collected from 20 normotensive pregnant women and 20 preeclamptic women, and NLRP3, caspase-1, IL-1 β , tumor necrosis factor-alpha (TNF- α ) , IL-18 and high-mobility group box 1 protein (HMGB1) were evaluated by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and also analyzed by quantitative real-time polymerase chain reaction (RT-qPCR). Results Placenta from pregnant women with PE showed increased mRNA expression for NLRP3, caspase-1, IL-1 β and TNF- α as well as their protein expression. Higher levels of caspase 1, IL-1 β and TNF- α were detected by ELISA in placental homogenate of preeclamptic group than in normotensive group. Lower expression of mRNA for IL-18 and its protein expression were detected in placenta of pregnant women with PE compared with normotensive group. No significant differences were observed between control and preeclamptic groups in relation to HMGB1 gene and protein expression. Conclusion The results suggest that placenta from pregnant women with preeclampsia shows activation of NLRP3 inflammasome which may be involved in the exaggerated inflammatory state detected in women with preeclampsia. Financial support: Fapesp 2012/24697-8 and 2013/00535-1
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