Figure 7. Proposed mechanism of estradiol regulation of NF-κB signaling in primary human macrophages.

(A) LPS binding to TLR4 induces expression of let-7a and decreases expression of miR-125b, leading to decreased expression of κB-Ras2 to enable complete activation of NF-κB signaling and TNF-α expression. (B) When macrophages are treated with estradiol prior to LPS stimulation, changes in expression of let-7a and miR-125b in response to 29LPS are abrogated. This results in up-regulation of κB-Ras2 and inhibition of NF-κB signaling, culminating in decreased expression of TNF-α.