Progesterone and vitamin D downregulate the activation of the NLRP1/NLRP3 inflammasomes and TLR4-MyD88-NF-κB pathway in monocytes from pregnant women with preeclampsia

Graphical abstract showing the immunomodulatory effect of progesterone (PG) and vitamin D (VD) on the inflammatory state of monocytes from preeclamptic women. Monocytes from women with PE show significantly higher basal or endogenous gene expression of NLRP1, NLRP3, caspase-1, TLR4, MyD88, and NF-κB. Both gene and protein expression of the inflammatory cytokines IL-1β, IL-18, and TNF-α, as well as the transcription factor NF-κB, were significantly higher in preeclamptic women.Treatment of monocytes with PG or VD showed that these hormones negatively regulate monocyte endogenous activation from preeclamptic women by decreasing the activation of NLRP1/NLRP3 inflammasome pathways and the TLR4/MyD88/NF-κB signalling axis.