Upregulation of TLR2 expression is induced by estrogen via an estrogen-response element (ERE)

• E2 upregulates TLR2 mRNA and protein level in differentiated THP-1 cell.
• The position −251 to −237 of TLR2 promoter contains an ER responsive element.
• TLR2 is an estrogen-regulated gene through the interaction of ERa with ERE.

TLR2 and estrogen are both thought to be involved in the pathogenesis of RA; however, it is unknown if there is an association between estrogen and TLR2. In this report, we treated PMA-differentiated THP-1 cells with 17β-estradiol (E2) and observed increases in TLR2 mRNA and protein levels by real-time quantitative PCR and western blot. Transfection of THP-1 cells with a series of 5′-deleted TLR2 promoter-luciferase constructs revealed that E2 enhanced TLR2 transcriptional activity in an estrogen receptor alpha (ERα)-dependent pattern. An estrogen receptor response element (ERE) was identified 251 bases upstream of the TLR2 promoter, and electrophoretic mobility shift assay and chromatin immunoprecipitations showed ERα binding was increased by E2. In summary, this work demonstrated that TLR2 is a new estrogen-regulated gene whose expression is upregulated through the interaction of ERα with an ERE in the promoter region.