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• W1703103639 abstract "Previous findings suggest that 17beta-estradiol (estradiol) has a suppressive effect on TNF-alpha, but the mechanism by which estradiol regulates TNF-alpha expression in primary human macrophages is unknown. In this article, we demonstrate that pretreatment of human macrophages with estradiol attenuates LPS-induced TNF-alpha expression through the suppression of NF-kappaB activation. Furthermore, we show that activation of macrophages with LPS decreases the expression of kappaB-Ras2, an inhibitor of NF-kappaB signaling. Estradiol pretreatment abrogates this decrease, leading to the enhanced expression of kappaB-Ras2 with LPS stimulation. Additionally, we identified two microRNAs, let-7a and miR-125b, which target the kappaB-Ras2 3' untranslated region (UTR). LPS induces let-7a and inhibits miR-125b expression in human macrophages, and pretreatment with estradiol abrogates these effects. 3'UTR reporter assays demonstrate that let-7a destabilizes the kappaB-Ras2 3'UTR, whereas miR-125b enhances its stability, resulting in decreased kappaB-Ras2 in response to LPS. Our data suggest that pretreatment with estradiol reverses this effect. We propose a novel mechanism for estradiol inhibition of LPS-induced NF-kappaB signaling in which kappaB-Ras2 expression is induced by estradiol via regulation of let-7a and miR-125b. These findings are significant in that they are the first to demonstrate that estradiol represses NF-kappaB activation through the induction of kappaB-Ras2, a key inhibitor of NF-kappaB signaling." @default.
• W1703103639 created "2016-06-24" @default.
• W1703103639 creator A5027892220 @default.
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• W1703103639 date "2010-05-01" @default.
• W1703103639 modified "2023-10-17" @default.
• W1703103639 title "Estradiol Suppresses NF-κB Activation through Coordinated Regulation of let-7a and miR-125b in Primary Human Macrophages" @default.
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• W1703103639 doi "https://doi.org/10.4049/jimmunol.0903463" @default.
• W1703103639 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2882792" @default.
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