Immunomodulatory Effects of 17β-Estradiol on Epithelial Cells during Bacterial Infections

Figure 4

Effects of E2 on bovine mammary epithelial cells during Staphylococcus aureus infection. During S. aureus infection in bovine mammary epithelial cells (bMECs), E2 inhibits the mitogen-activated protein kinases (MAPKs), resulting in anti-inflammatory effects (decreasing gene expression of IL-1β and IL-6 as well as increasing gene expression of IL-10). E2 also actives protein kinase B (Akt), which in turn activates transcriptional factors, such as activator protein 1 (AP-1), NF1, or ER, that are related to IIR gene expression, such as AMPs, IL-10, or TNF-α. Through the zipper mechanism, S. aureus is internalized into epithelial cells, preventing it from being detected by the defense system of the host cell. However, E2 can block the signaling pathway of the zipper mechanism through the inhibition of focal adhesion kinase (FAK), resulting in the reduction of S. aureus internalization. The production of antimicrobial molecules (e.g., antimicrobial peptides) by bMECs treated with E2 also reduces S. aureus viability. However, the identity of the AMPs secreted by bMECs remains unknown. By RT-qPCR, the upregulation in the gene expression of DEFB1 (defensin beta 1), BNBD5 (bovine neutrophil beta-defensin 5), and S100A7 (psoriasin) has been shown. E2 induces the expression of TLR2, a key receptor in the recognition of S. aureus, as well as upregulates the expression of its receptors (ERα/β) [54, 58, 60].