Silibinin downregulates the expression of the Th1 and Th17 profiles by modulation of STATs and transcription factors in pregnant women with preeclampsia

Abstract

Preeclampsia (PE) is a multifactorial disease that is characterized by inflammation. Some of the factors responsible for this inflammation are the cells of the innate and adaptive immune systems and their interactions. The use of natural products, such as silibinin (SB), can contribute to the control of this inflammation and gestational success. The present study evaluated whether the flavonoid SB has an in vitro immunomodulatory effect on the signal transducers and transcription activators (STATs) signaling pathway and transcription factors of CD4+ T cell subsets obtained from preeclamptic and normotensive (NT) pregnant women. Peripheral blood mononuclear cells (PBMCs) from 18 preeclamptic and 18 NT pregnant women were cultured with and without SB to analyze the expression of STATs and transcription factors by flow cytometry, and cytokines were measured in the culture supernatant by ELISA. The results showed that treating cells with SB decreased STAT1/ STAT4/T-bet and STAT3/RORγt, which characteristic of Th1 and Th17 inflammatory profiles, as well as increased STAT6/GATA-3 and STAT5/FoxP3 of anti-inflammatory and regulatory profiles, respectively. In addition, PBMCs from preeclamptic women treated with SB released lower concentrations of inflammatory cytokines and higher levels of IL-10 and TGF-β. Therefore, SB plays an immunomodulatory role on CD4+ T cell subsets in PE, leading to the downregulation of inflammatory profiles and upregulation of anti-inflammatory and regulatory profiles. More studies are necessary to better understand the modulation of CD4+ T cell subsets by the JAK/STAT and NF-κB pathways in this gestational pathology.