The intervention effect of aspirin on a lipopolysaccharide-induced preeclampsia-like mouse model by inhibiting the nuclear factor-κB Pathway

• Published in: Biology of reproduction Vol. 99; no. 2; pp. 422 - 432
• Main Authors: Li, Guanlin, Ma, Liyang, Lin, Li, Wang, Yan-ling, Yang, Huixia
• Format: Journal Article
• Language: English
• Published: United States Society for the Study of Reproduction 01.08.2018; Oxford University Press
• Subjects: inflammatory factor; lipopolysaccharide; low-dose aspirin; nuclear factor-κB; Preeclampsia; PREGNANCY; Reproductive health; Rodents; nuclear factor-κB; inflammatory factor; preeclampsia; lipopolysaccharide; low-dose aspirin
• ISSN: 0006-3363; 1529-7268; 1529-7268
• DOI: 10.1093/biolre/ioy025

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.