Placental Fractalkine Is Up-Regulated in Severe Early-Onset Preeclampsia

Abstract

The pathogenesis of preeclampsia (PE) includes the release of placental factors into the maternal circulation, inducing an inflammatory environment in the mother. One of the factors may be the proinflammatory chemokine fractalkine, which is expressed in the syncytiotrophoblast of human placenta, from where it is released into the maternal circulation by constitutive shedding. We examined whether placental fractalkine is up-regulated in severe early-onset PE and whether the proinflammatory cytokines tumor necrosis factor (TNF)-α and IL-6 are able to increase the expression of fractalkine. Gene expression analysis, enzyme-linked immunosorbent assay, and immunohistochemistry consistently showed increased fractalkine expression in placentas from severe early-onset PE, compared to gestational age-matched controls. Expression of a disintegrin and metalloproteinases (ADAMs) 10 and 17, which convert transmembrane fractalkine into the soluble form, was significantly increased in these cases. Incubation of first-trimester placental explants with TNF-α provoked a significant increase in fractalkine expression and release of the soluble form, whereas IL-6 had no effect. TNF-α-mediated up-regulation of placental fractalkine was reversed in the presence of the aspirin-derivative salicylate, which impaired activation of NF-κB p65 in TNF-α-treated explants. On the basis of data from placental explants, we suggest that increased maternal TNF-α may up-regulate the expression and release of placental fractalkine, which, in turn, may contribute to an exaggerated systemic inflammatory response in PE.

Placental expression of AChE, α7nAChR and NF-κB in patients with preeclampsia

“…These results implied the pathological role of NF-κB in PE, whose expression intensity reflects the severity of PE. This agrees with the findings in many other studies [27][28][29]. The pathogenesis of PE may be related to the activation of NF-κB, which in turn participates in microvascular wall remodeling and placental vascular inflammation.…”

Magnesium Sulfate Prevents Placental Ischemia-Induced Increases in Brain Water Content and Cerebrospinal Fluid Cytokines in Pregnant Rats

“…Future studies will determine whether placental ischemia is associated with increased glutamate signaling. A recent study showed that placental fractalkine levels are increased in severe early preeclampsia patients (Siwetz et al, 2015). Because fractalkine can reduce GABAergic function in pyramidal neurons in patients with mesial temporal lobe epilepsy (Roseti et al, 2013), it is possible that MgSO 4 may exert its anti-seizure effects through reduced fractalkine levels.…”

Platelet-derived factors impair placental chorionic gonadotropin beta-subunit synthesis

“…Thereafter, sections were stained using a staining robot (Autostainer 360; Thermo Fisher Scientific) with primary antibodies as indicated in Suppl. Table 3 using the UltraVision Large Volume Detection System HRP Polymer Kit (Thermo Fisher Scientific) as previously described [3,44].…”