[184-POS]: NLRP3 inflammasome induced by uric acid in monocytes from pregnant women with preeclampsia

Mariana L Matias, Mariana Romao, Ingrid C Weel, Priscila R Nunes, Vera T M Borges, Leandro G de Oliveira, Joao P Araujo, Jose C Peracoli, Maria T S Peracoli
Pregnancy Hypertension 2015, 5 (1): 94

OBJECTIVES: Preeclampsia (PE) is characterized by a state of abnormal activation of the innate immune system. This pathology is associated with hyperuricemia, elevated serum levels of inflammatory cytokines and oxidative stress.Uric acid crystals can activate the inflammasome, a multi-protein complex important for processing and releasing of interleukin-1beta (IL-1beta) and IL-18. This study investigated the endogenous or monosodium urate-induced activation of monocytes from pregnant women with PE by NLRP1/NLRP3 inflammasome identification in these cells as well as association of this complex with IL-1beta, IL-18 and TNF-alpha expression by these cells.

METHODS: Monocytes (5×105cell/mL) were obtained from 20 preeclamptic, 15 normotensive (NT) pregnant women, in the last trimester of pregnancy, and 10 non-pregnant (NP) women. The presence of inflammasome 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 stimulation with monosodium urate (MSU) (stimulated expression). Results were analyzed by non-parametric tests with significance level set at 5%.

RESULTS: In the absence of stimulation, the basal mRNA expression of NLRP3, IL-1beta and TNF-alpha in monocytes was significantly higher in PE than in NT and NP groups. Gene expression of caspase-1 was increased while IL-18 expression was lower in PE compared with NT and NP groups. No alteration was observed in NLRP1 expression. An increase in NLRP3 mRNA was detected after preeclamptic patients monocytes stimulation with MSU, while no alteration was detected 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 by the disease process. NLRP3 gene expression in monocytes from women with PE stimulated with MSU suggests that hyperuricemia contributes to the inflammasome involvement in PE pathogenesis. Financial support - FAPESP 2012/21287-3 and 2012/24697-8.

DISCLOSURES: M.L. Matias: None. M. Romao: None. I.C. Weel: None. P.R. Nunes: None. V.T. Borges: None. L.G. de Oliveira: None. J.P. Araujo Jr.: None. J.C. Peracoli: None. M.T. Peracoli: None.

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