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SOJ Immunol. 2014 Jan 20;2(1). pii: 07.

Estrogen Receptor Alpha Binding to ERE is Required for Full Tlr7- and Tlr9-Induced Inflammation.

Author information

  • 1Division of Rheumatology and Immunology, Medical University of South Carolina, USA.
  • 2Ralph H. Johnson Veterans Affairs Hospital, Charleston, South Carolina, USA.

Abstract

We previously found that a maximum innate inflammatory response induced by stimulation of Toll-like receptors (TLRs) 3, 7 and 9 requires ERα, but does not require estrogen in multiple cell types from both control and lupus-prone mice. Given the estrogen-independence, we hypothesized that ERα mediates TLR signaling by tethering to, and enhancing, the activity of downstream transcription factors such as NFκB, rather than acting classically by binding EREs on target genes. To investigate the mechanism of ERα impact on TLR signaling, we utilized mice with a knock-in ERα mutant that is unable to bind ERE. After stimulation with TLR ligands, both ex vivo spleen cells and bone marrow-derived dendritic cells (BM-DCs) isolated from mutant ERα ("KIKO") mice produced significantly less IL-6 compared with cells from wild-type (WT) littermates. These results suggest that ERα modulation of TLR signaling does indeed require ERE binding for its effect on the innate immune response.

KEYWORDS:

DCs; ERα; TLRs

PMID:
25061615
PMCID:
PMC4106444
DOI:
10.15226/soji.2014.00107
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