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Estrogen Receptor Alpha Modulates Mesangial Cell Responses to Toll-Like Receptor Ligands.
MedLine Citation:
PMID:  25343264     Owner:  NLM     Status:  Publisher    
: The female predominance in lupus is incompletely understood. The mechanisms for this difference are multifactorial involving the sex chromosomes, the hormones, and their receptors. We, and others, demonstrated that estrogen receptor alpha (ERα)-deficient female mice developed significantly less lupus-like renal disease. This protective effect of ERα deficiency occurred despite no impact on glomerular immune complex deposition. We hypothesized that decreased renal disease in ERα-deficient mice was due to a dampened renal response to inflammatory stimuli. Given the role of Toll-like receptors (TLRs) in lupus, we assessed whether there was an interaction between TLR responses and ERα. Herein, we show that TLR3, 4, and 7 ligands all enhanced mesangial cell (MC) ERα expression, whereas neither estrogen, nor ERα, impacted TLR3, 4, or 7 expression in MCs. The lack of ERα markedly decreased MC production of interleukin 6 and monocyte chemoattractant protein 1 (MCP-1) following addition of TLR3, 4, and 7 ligands. In MCs, TLR ligands induced ERα phosphorylation and nuclear localization. TLR3-induced nuclear factor κB nuclear translocation in MCs was not significantly affected by estrogen or ERα. Finally, we demonstrate that female MCs express more TLR3 and respond to TLR ligands with a significantly increased production of interleukin-6 compared with male MCs. These results identify a significant impact/interaction of ERα in TLR-mediated inflammatory responses in MCs.
John Svenson; Melissa Cunningham; Subhajit Dasgupta; Gary S Gilkeson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-23
Journal Detail:
Title:  The American journal of the medical sciences     Volume:  -     ISSN:  1538-2990     ISO Abbreviation:  Am. J. Med. Sci.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-24     Completed Date:  -     Revised Date:  2014-10-25    
Medline Journal Info:
Nlm Unique ID:  0370506     Medline TA:  Am J Med Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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