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[37-OR]: The role of hyaluronan in NLRP3 inflammasome in monocytes from pregnant women with preeclampsia.

OBJECTIVES: Preeclampsia (PE) is considered as a major cause of both maternal and fetal morbidity and mortality. Plasma of preeclampsia women has elevated levels of molecular structures associated with stress and cell death, such as hyaluronan (HA), which bind to receptors present in cells of innate immunity and activate an intracellular complex called inflammasome. This study investigated the state of activation both endogenous and induced by HA in monocytes of these patients, by identifying the presence of NLRP1/NLRP3 and its association with IL-1beta, IL-18 and TNF-alpha.

METHODS: Monocytes (5×10(5)cell/mL) were obtained from 15 preeclamptic (PE), 15 normotensive (NT) pregnant women and 10 non-pregnant (NP) women. The presence of inflammasome in these cells was evaluated by gene expression of NLRP3, NLRP1, caspase-1, IL-1beta, IL-18 and TNF-alpha by quantitative real-time PCR (RT-qPCR) (endogenous expression) or after in vitro activation with HA (stimulated expression). Differences among groups were analyzed by non-parametric tests with significance level set at 5%.

RESULTS: In the absence of monocytes stimulation mRNA expression of NLRP3, IL-1beta and TNF-alpha was significantly higher in PE group than in NT and NP groups. mRNA expression of caspase-1 was increased in PE group compared with NT group, while IL-18 mRNA expression was lower in PE than NT and NP groups. No alteration was observed in NLRP1 expression. HA stimulation led to an increase in NLRP3, IL-1beta and TNF-alpha mRNA expression in monocytes from PE group than in NT and NP groups.

CONCLUSIONS: The basal up-regulation of NLRP3, caspase-1, IL-1beta and TNF-alpha mRNA expression in monocytes from preeclamptic women confirms the activated profile of these cells in PE. The higher gene expression of inflammasome by HA stimulation suggests that this component of extracellular matrix may contribute to inflammasome generation in monocytes from preeclamptic women. Financial support - FAPESP 2013/00534-5 and 2012/24697-8 DISCLOSURES: M. Romao: None. M.L. Matias: None. I.C. Weel: None. C.J. Fernandes: None. V.T. Borges: None. J.P. Araujo Jr: None. J.C. Peracoli: None. M.T. Peracoli: None.

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