Treatment of Lipoxin A4 and its analogue on low-dose endotoxin induced preeclampsia in rat and possible mechanisms

Preeclampsia (PE) is known to represent an exaggerated maternal inflammatory response to pregnancy. Lipoxin A4 (LXA4), considered as an endogenous stop signal in inflammation, has been extensively studied pre clinically for its inflammatory pro-resolving effects. Thus, in the current study, we tested the effect of BML-111 (synthetic analogue of LXA4) on experimental PE rats induced by low-dose endotoxin (LPS) and of LXA4 on human extravillous trophoblast cell line (TEV-1). In vivo experiment results showed that systolic blood pressure, 24 h-urinary albumin excretion, serum TNF-α and IL-8 levels and morphologic damage of placenta and kidney caused by LPS were all effectively alleviated by BML-111. LXA4 also inhibited LPS-triggered apoptosis, activation of NF-κB, TNF-α and IL-8 mRNA and protein expression in TEV-1 cells. At the same time, BML-111 protected the cells from LPS-reduced proliferation. The current study demonstrated for the first time that LXA4 could alleviate the symptoms of PE in endotoxin exposed rats.

► BML-111, an analogue of Lipoxin A4, could alleviate the symptoms of preeclamptic rats through inhibition on inflammatory response in placenta.
► Lipoxin A4 inhibits LPS-induced cell apoptosis, TNF-α and IL-8 mRNA and protein expression in human extravillous trophoblast cell line.
► Lipoxin A4 inhibits LPS-induced nuclear translocation of NF-κB in human extravillous trophoblast cell line.