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• W1566261912 endingPage "1783" @default.
• W1566261912 startingPage "1776" @default.
• W1566261912 abstract "NF-kappaB plays a major role in regulating the immune system. Therefore, alterations in NF-kappaB activity have profound effects on many immunopathologies, including inflammation, autoimmunity, and lymphoid neoplasia. We investigated the effects of estrogen (17beta-estradiol) on NF-kappaB in C57BL/6 mice since estrogen is a natural immunomodulator and we have recently reported that estrogen up-regulates several NF-kappaB-regulated proteins (inducible NO synthase, IFN-gamma, and MCP-1). We found that in vivo estrogen treatment had differential effects on NF-kappaB family members. Estrogen profoundly blocked the nuclear translocation of p65, c-Rel, and Rel-B, partially blocked p52, but permitted translocation of p50. Despite blockade of both the classical (p65/p50) and alternative (RelB/p52) NF-kappaB activation pathways, estrogen induced constitutive NF-kappaB activity and increased the levels of cytokines regulated by NF-kappaB (IL-1 alpha, IL-1 beta, IL-10, and IFN-gamma). Studies involving a NF-kappaB inhibitor confirmed a positive regulatory role of NF-kappaB on these cytokines. Remarkably, estrogen selectively induced B cell lymphoma 3 (Bcl-3), which is known to associate with p50 to confer transactivation capabilities, thereby providing a potential link between observed p50 DNA-binding activity and estrogen up-regulation of NF-kappaB transcriptional activity. Chromatin immunoprecipitation assays confirmed that Bcl-3 bound to the promoter of the NF-kappaB-regulated inducible NO synthase gene in cells from estrogen-treated mice. Estrogen appeared to act at the posttranscriptional level to up-regulate Bcl-3 because mRNA levels in splenocytes from placebo- and estrogen-treated mice were comparable. The novel findings of differential regulation of NF-kappaB proteins by estrogen provide fresh insight into potential mechanisms by which estrogen can regulate NF-kappaB-dependent immunological events." @default.
• W1566261912 created "2016-06-24" @default.
• W1566261912 creator A5042044088 @default.
• W1566261912 creator A5047415405 @default.
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• W1566261912 date "2007-08-01" @default.
• W1566261912 modified "2023-10-09" @default.
• W1566261912 title "Despite Inhibition of Nuclear Localization of NF-κB p65, c-Rel, and RelB, 17-β Estradiol Up-Regulates NF-κB Signaling in Mouse Splenocytes: The Potential Role of Bcl-3" @default.
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• W1566261912 doi "https://doi.org/10.4049/jimmunol.179.3.1776" @default.
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