Linked Life Data

17641044

Source:http://linkedlifedata.com/resource/pubmed/id/17641044

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-7-20
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
179
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1776-83
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17641044-Active Transport, Cell Nucleus, pubmed-meshheading:17641044-Animals, pubmed-meshheading:17641044-Cell Nucleus, pubmed-meshheading:17641044-Cells, Cultured, pubmed-meshheading:17641044-Dimerization, pubmed-meshheading:17641044-Estradiol, pubmed-meshheading:17641044-Male, pubmed-meshheading:17641044-Mice, pubmed-meshheading:17641044-Mice, Inbred C57BL, pubmed-meshheading:17641044-NF-kappa B p50 Subunit, pubmed-meshheading:17641044-Proto-Oncogene Proteins, pubmed-meshheading:17641044-Proto-Oncogene Proteins c-rel, pubmed-meshheading:17641044-Signal Transduction, pubmed-meshheading:17641044-Spleen, pubmed-meshheading:17641044-Transcription Factor RelA, pubmed-meshheading:17641044-Transcription Factor RelB, pubmed-meshheading:17641044-Transcription Factors, pubmed-meshheading:17641044-Up-Regulation
pubmed:year
2007
pubmed:articleTitle
Despite inhibition of nuclear localization of NF-kappa B p65, c-Rel, and RelB, 17-beta estradiol up-regulates NF-kappa B signaling in mouse splenocytes: the potential role of Bcl-3.
pubmed:affiliation
Department of Biomedical Sciences and Pathology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural