Nunes Priscila R, Romao-Veiga Mariana, Matias Mariana L, Ribeiro Vanessa R, de Oliveira Leandro, Peracoli Jose Carlos, Terezinha S Peracoli Maria
Botucatu Medical School, Sao Paulo State University (Unesp), Botucatu, Sao Paulo, Brazil.
Botucatu Medical School, Sao Paulo State University (Unesp), Botucatu, Sao Paulo, Brazil.
Hum Immunol. 2022 Jan;83(1):74-80. doi: 10.1016/j.humimm.2021.10.002. Epub 2021 Oct 23.
This study aimed to evaluate the immunomodulatory effect of vitamin D (VD) on the NLRP1 and NLRP3 inflammasomes in placental explants from preeclamptic (PE) and normotensive (NT) pregnant women. Placental explants from eight PE and eight NT pregnant women were cultured with or without hydrogen peroxide (HO) VD or HO + VD. Gene and protein expression of NLRP1, NLRP3, HMGB1, caspase-1, IL-1β, TNF-α and IL-18 were determined by qPCR and Western blotting/ELISA. Compared to NT pregnant women, the endogenous gene expression of NLRP1, NLRP3, HMGB1, IL-1β, TNF-α and IL-18 was significantly higher in explants from PE and became decreased after VD treatment. Similarly, VD decreased the protein expression of NLRP1, NLRP3, caspase-1, HMGB1, IL-1β, TNF-α and IL-18 in PE. Placental explants from NT cultured with HO showed increased gene and protein expression of NLRP1, NLRP3, caspase-1, IL-1β, TNF-α and HMGB1, while HO was also able to increase TNF-α and caspase-1 gene expression in PE. Treatment with HO + VD decreased gene/protein expression of NLRP1, NLRP3, caspase-1, HMGB1, IL-1β, TNF-α and IL-18 in PE and NT explants with HO. NLRP1 and NLRP3 are upregulated in the PE. VD may play an immunomodulatory role in the placental inflammation and downregulates oxidative stress induced in vitro by HO
本研究旨在评估维生素D（VD）对先兆子痫（PE）和血压正常（NT）孕妇胎盘外植体中NLRP1和NLRP3炎性小体的免疫调节作用。将8例PE孕妇和8例NT孕妇的胎盘外植体分别在有或无过氧化氢（HO）、VD或HO + VD的条件下培养。通过qPCR以及蛋白质免疫印迹法/酶联免疫吸附测定法测定NLRP1、NLRP3、高迁移率族蛋白B1（HMGB1）、半胱天冬酶 - 1、白细胞介素 - 1β（IL - 1β）、肿瘤坏死因子 - α（TNF - α）和白细胞介素 - 18（IL - 18）的基因和蛋白表达。与NT孕妇相比，PE胎盘外植体中NLRP1、NLRP3、HMGB1、IL - 1β、TNF - α和IL - 18的内源性基因表达显著更高，且VD处理后降低。同样，VD降低了PE中NLRP1、NLRP3、半胱天冬酶 - 1、HMGB1、IL - 1β、TNF - α和IL - 18的蛋白表达。用HO培养的NT胎盘外植体显示NLRP1、NLRP3、半胱天冬酶 - 1、IL - 1β、TNF - α和HMGB1的基因和蛋白表达增加，而HO也能够增加PE中TNF - α和半胱天冬酶 - 1的基因表达。用HO + VD处理可降低HO处理的PE和NT胎盘外植体中NLRP1、NLRP3、半胱天冬酶 - 1、HMGB1、IL - 1β、TNF - α和IL - 18的基因/蛋白表达。NLRP1和NLRP3在PE中上调。VD可能在胎盘炎症中发挥免疫调节作用，并下调HO体外诱导的氧化应激
