P 13 Inflammasome downregulation by silibinin and vitamin D in monocytes from pregnant women with preeclampsia

Preeclampsia (PE) is characterized by a state of abnormal activation of the innate immune system. This pathology is associated with activation of inflammasome, a multi-protein structure which is important for processing and release of inflammatory cytokines such as interleukin-1 beta (IL-1β) and IL-18. The imbalance between pro- and anti-inflammatory cytokines in PE seems to be dependent on the deficiency of regulatory factors capable of modulating inflammatory response. This imbalance could be improved by administration of substances with anti-inflammatory and modulatory properties such as silibinin (SB) and vitamin D (VD). The aim of this study was to evaluate the modulatory effect of silibinin and vitamin D on NLRP1 and NLRP3 inflammasomes in monocytes from pregnant women with PE. MethodsMonocytes obtained from peripheral blood of 20 pregnant women with PE and 20 normotensive (NT) pregnant women were cultured in the presence or absence of silibinin or vitamin D and the expression of NLRP1, NLRP3, CASP1, TLR4, MYD88, NFKB1, IL1B, IL18, TNF and IL10 were assayed by qPCR and the concentrations of cytokines were determined by ELISA. Results were analyzed by non-parametric tests at 5% significance level. The basal expression of inflammation-related genes was significantly higher while IL-10 gene expression was lower in monocytes from preeclamptic group than in NT group. These cells treatment with SB and VD led to decrease in the expression of the inflammatory genes and to an increase in mRNA IL-10 in PE group. Basal levels of TNF-α and IL-1β were elevated in monocytes cultures from preeclamptic women and decreased after SB and VD treatment. The basal up-regulation of NLRP1, NLRP3, caspase-1, TLR4, MyD88, NF-κB, IL-1β, IL-18 and TNF-α mRNA expression in monocytes from PE group confirms the inflammatory profile activation of these cells. SB and VD treatment decreased the expression of inflammation-related genes and inflammatory cytokines production by monocytes from pregnant women with PE, suggesting that these modulators may contribute to inflammasome downregulation in preeclampsia.