Expression and Localization of TLR4 and Its Negative Regulator Tollip in the Placenta of Early-Onset and Late-Onset Preeclampsia

Objective. Toll-like receptor 4 (TLR4) is a key component of the innate arm of the immune system that mediates inflammatory responses following exposure to bacterial lipopolysaccharides. In doing so, TLR4 may contribute to the pathogenesis of preeclampsia (PE). We sought to assess the spatio-temporal expression of TLR4 and its negative regulator Toll-interacting protein (Tollip) in placental tissues from normal and preeclamptic pregnancies. Methods. Using immunohistochemistry and immunoblotting, we investigated the localization of TLR4 and its negative regulator Tollip in first- and third-trimester human placenta. Results. TLR4 was found to be expressed in the cytoplasm of trophoblasts in both first- (n = 6) and third-trimester (n = 24) placental villous samples. Tollip was mainly located in the cytoplasm of cytotrophoblasts in the first-trimester placental tissues; in contrast, our analyses of third-trimester placental tissues demonstrated that Tollip was mainly located in the decidual cells. Using western blot analysis, TLR4 expression was shown to be significantly higher in early-onset PE tissues than control group placentas (n = 8 for each group, p < 0.01). However, we were unable to detect a significant difference between late-onset PE and normal controls (n = 8 for each group, p = 0.119). Conclusion. These data demonstrate the novel observation that TLR4 may play a much more important role in early-onset PE. Interestingly, the spatial expression of Tollip at different stages of gestation may play an important role in the pathophysiology of PE.