Fig. 7
Schematic diagram of E2-activated SGK1 in priming anti-inflammatory M2 phenotype of macrophages at the maternal–fetal interface. Activation of SGK1 by E2 via the ERβ and PI3K signaling pathways elicits the M2 macrophage subtype, leading to elevated secretion of Th2 cytokines by increasing the expression levels of ARG1 and IRF4. By contrast, SGK1 inhibition promotes pro-inflammatory cytokine productions by activating NF-κB in LPS-stimulated macrophages. Therefore, E2-sensitive activation of SGK1 contributes to anti-inflammatory M2 macrophage polarization and Th2 skewing at the maternal–fetal interface. E2, estradiol; SGK1, serum-glucocorticoid regulated kinase; PI3K, phosphoinositide 3-kinase; ER, estrogen receptor; NF-κB; nuclear factor kappa B; IκBα, inhibitor of nuclear factor kappa-B kinase subunit alpha; ARG1, arginase 1; IRF4, immune regulatory factor 4; LPS, lipopolysaccharide; IL, interleukin; IFN-γ, interferon gamma; MMP9, matrix metalloproteinase 9; VEGF-A, vascular endothelial growth factor A; TNF, tumor necrosis factor; IL, interleukin