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Estrogen Receptor Alpha Binding to ERE is Required for Full Tlr7- and Tlr9-Induced Inflammation
Authors: Melissa A Cunningham, Jena Wirth, Osama Naga, Jackie Eudaly and Gary S Gilkeson
Number of views: 285
We previously found that a maximum innate inflammatory
response induced by stimulation of Toll-like Receptors (TLRs) 3, 7
and 9 requires ERa, but does not require estrogen in multiple cell
types from both control and lupus-prone mice. Given the estrogenindependence,
we hypothesized that ERa mediates TLR signaling by
tethering to, and enhancing, the activity of downstream transcription
factors such as NFkB, rather than acting classically by binding EREs
on target genes. To investigate the mechanism of ERa impact on TLR
signaling, we utilized mice with a knock-in ERa 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 ERa (“KIKO”) mice produced significantly less IL-6
compared with cells from Wild-Type (WT) littermates. These results
suggest that ERa modulation of TLR signaling does indeed require
ERE binding for its effect on the innate immune response.