Estrogen Suppresses Cytokines Release in cc4821 Infection TLR4 and ERβ-p38-MAPK Pathway.

Estrogen has long been known to possess immune-modulatory effects in diseases, and multiple pathological conditions show great sex disparities. However, the impact of estrogen in infection has not been determined. The present study aimed to investigate the role of estrogen in infection and the molecular mechanism. We selected 35 isolates representing different clonal complexes (cc), serogroups, and isolation sources to infect the HBMEC cell line. Results showed that the expression of estrogen receptor (ER) β in -infected cells was downregulated compared with that in normal cells. The expression of ERβ induced by invasive isolates was lower than that in carriers. Serogroup C isolates induced the lowest expression of ERβ compared with serogroup A and B isolates. We used four cc4821 isolates to infect two kinds of host cells (human brain microvascular endothelial cells and meningeal epithelial cells). The results showed that 17 β-estradiol (E2) could inhibit the release of inflammatory factors interleukin (IL)-6, IL-8, and tumor necrosis factor-α after infection TLR4. E2 could inhibit the activation of the p38-MAPK signal pathway induced by infection through binding to ERβ, and significantly inhibit the release of inflammatory factors in -infected host cells. This study demonstrated that estrogen plays a protective role in infection. ERβ is potentially associated with the release of inflammatory cytokines in infection, which sheds light on a possible therapeutic strategy for the treatment of invasive diseases caused by .