Estradiol Suppresses TLR4-triggered Apoptosis of Decidual Stromal Cells and Drives an Anti-inflammatory TH 2 Shift by Activating SGK1

International Journal of Biological Sciences
Yiyun LouFan Jin

Abstract

A pro-inflammatory cytokine profile at the feto-maternal interface may predispose immune maladaptation notably in early miscarriages. We investigated the involvement of estradiol (E2)-activated serum-glucocorticoid regulated kinase 1 (SGK1) in preserving the tolerogenic and pro-survival intrauterine microenvironment beneficial to gestation maintenance. Decidual SGK1 was down-regulated in early miscarriage, consistent with the lower serum E2 concentration seen in pregnancy loss. Lipopolysaccharide (LPS)/Toll-like receptors 4 (TLR4) signaling induced apoptosis and the pro-inflammatory T helper type (TH) 1 response of decidual stromal cells (DSCs) were associated with miscarriage. SGK1 activation was suppressed by LPS/TLR4 signaling and would be rescued by E2 administration via the PI3K signaling pathway in DSCs. SGK1 activation attenuated TLR4-mediated cell apoptosis, while promoting cell viability of DSCs by up-regulating the pro-survival genes BCL2 and XIAP, and enhancing the phosphorylation of FOXO1. Furthermore, E2-induced SGK1 activation reduced the secretion of pro-inflammatory TH1 cytokines, and promoted the generation of TH2 cytokines and elevated IRF4 mRNA and protein levels in LPS-incubated DSCs. Pharmacologic inhibitio...Continue Reading

Citations

Feb 23, 2019·Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology·Nancy Noyola-MartínezDavid Barrera
Jun 28, 2018·Frontiers in Immunology·Oxana BereshchenkoCarlo Riccardi
Jul 19, 2020·International Immunopharmacology·Roghayeh JafarpourMorteza Motallebnezhad
Aug 28, 2021·International Journal of Molecular Sciences·Sheng-Dean LuoChing-Shuen Wang

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Methods Mentioned

BETA
confocal microscopy
nuclear translocation
electrophoresis
flow cytometry
transfection

Software Mentioned

Bandscan
Statistical Package for SocialSciences

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