122. Silibinin regulates the NF-κB pathway and NLRP1/NLRP3 inflammasomes induced by monosodium urate in monocytes from preeclamptic women and THP-1 cells

Abstract

Introduction Preeclampsia (PE) is characterized by a state of abnormal activation of the innate immune system. It’s associated with hyperuricemia and elevated serum levels of inflammatory cytokines. Uric acid crystals can activate inflammasome, a multiprotein structure important for processing and release of inflammatory cytokines. 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, which could be alleviated by administration of substances with anti-inflammatory and modulatory properties such as silibinin (SB). Objective The study aimed to evaluate the modulatory effect of silibinin on NLRP1 and NLRP3 inflammasomes and on NF-κB pathway activation in monocytes from preeclamptic women stimulated with monosodium urate (MSU). Methods Twenty preeclamptic women, 20 normotensive pregnant women (NT) and THP-1 cells were cultured with or without SB and MSU. Gene expression of NLRP1, NLRP3, Caspase-1, TLR4, MyD88, NF-κB, IL-1β, IL-18, TNF-α and IL-10 was performed by qPCR. Inflammatory cytokines and p65NF-κB activity were evaluated by ELISA. Results Monocytes of preeclamptic women presented higher endogenous activation of the inflammatory genes, as well as p65NF-κB basal activity and the inflammatory cytokines production than NT group. MSU stimulation increased the expression of these parameters, whereas SB treatment reduced them. Additionally, THP-1 cells had a similar immunological response profile of monocytes from preeclamptic women when cultured with or without MSU and SB. Conclusion These results suggest the MSU participation in the systemic inflammatory response, characteristic of preeclampsia, and that silibinin treatment is capable of modulating the sterile inflammation established in monocytes of preeclamptic women, demonstrating that this flavonoid plays a relevant role in the regulation of the inflammatory response in preeclampsia. Financial support FAPESP 2015/26147-3, 2016/18155-9 and 2016/22854-0