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27 April 2018 The intervention effect of aspirin on a lipopolysaccharide-induced preeclampsia-like mouse model by inhibiting the nuclear factor-κB Pathway
Guanlin Li, Liyang Ma, Li Lin, Yan-ling Wang, Huixia Yang
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Abstract

Preeclampsia is a severe pregnancy-related disorder, and patients usually present with high circulating inflammatory factor levels and excessive activation of the nuclear factor-κB (NF-κB) pathway. Administration of aspirin (ASP) is effective for preventing preeclampsia, and thus, we propose that ASP might affect placental function by regulating the NF-κB pathway. Systemic lipopolysaccharide (LPS) (20 µg/kg) was used to induce preeclampsia-like pregnant mouse model, and low-dose ASP (15.2mg/kg) was administrated. Here, we report significantly increased circulatory expression levels of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-6, and soluble Fms-related tyrosine kinase-1 in LPS-treated pregnant mice, accompanied by kidney and placental dysfunction. Low-dose ASP treatment significantly reversed the preeclampsia-like phenotype, lowering hypertension, decreasing proteinuria, and ameliorating fetal growth retardation. Moreover, the excessive activation of NF-κB signaling in mice placentae induced by LPS was significantly reduced by ASP. In JEG-3 cells, LPS activated the NF-κB signaling pathway by upregulating the expression of cyclooxygenase-2 (COX-2) and related inflammatory factors, whereas the invasion ability of JEG-3 cells was weakened. However, ASP administration impeded NF-κB signaling activation, downregulated COX-2 and inflammatory factor expression, and rescued trophoblast invasion. This study provides new evidence that low-dose ASP is beneficial for preeclampsia prevention by inhibiting NF-κB and its downstream signaling pathways in trophoblast cells.

Summary Sentence

Low-dose ASP is beneficial for preventing LPS-induced preeclampsia by inhibiting NF-κB and downstream signaling pathways in trophoblast cells.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Guanlin Li, Liyang Ma, Li Lin, Yan-ling Wang, and Huixia Yang "The intervention effect of aspirin on a lipopolysaccharide-induced preeclampsia-like mouse model by inhibiting the nuclear factor-κB Pathway ," Biology of Reproduction 99(2), 422-432, (27 April 2018). https://doi.org/10.1093/biolre/ioy025
Received: 10 October 2017; Accepted: 26 April 2018; Published: 27 April 2018
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