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

Cytokines, angiogenic, and antiangiogenic factors and bioactive lipids in preeclampsia

“…Both endoglin and sFlt-1 augment NO deficiency (188,189). Furthermore, lipoxins inhibited proliferation of macrophages and secretion of TNF-α in preeclampsia in a dose-dependent manner (190); lipoxin A4 suppressed IL-1β production of monocytes from severe preeclampsia women by inhibiting extracellular calcium influx (191); aspirin-triggered lipoxin A4 (ATL) reduced human PMN-endothelial cell adhesion when human PMN were incubated with ATL prior to addition to endothelial monolayers (192); and BML-111 (synthetic analogue of LXA4) effectively alleviated experimental preeclampsia induced by lowdose endotoxin (LPS) in rats and inhibited LPS-triggered apoptosis, activation of NF-κB, TNF-α and IL-8 mRNA and protein expression in human extravillous trophoblast (TEV-1) cells (193).…”

Lipoxin A4 Suppresses Lipopolysaccharide-Induced Hela Cell Proliferation and Migration via NF-κB Pathway

“…Our precious study found that lipoxins, which is so-called "stop signal" of inflammation, might also play a role in regulating genesis and development of tumors [6,7,9]. Moreover, LXA 4 could inhibit angiogenesis in human umbilical vein endothelial cells (HUVECs) [10,11]; inhibit HepG2 cell invasion induced by HGF [12]; play an important role in preeclampsia, fetal growth restriction, and embryo implantation [13][14][15]; and could downregulate expression of cyclooxygenase-2 in LPS-stimulated lung fibroblasts [16]. Recently, our group found that LXA 4 could inhibit NF-κB activation and cell cycle progression in RAW264.7 cells [17], and the analog of LXA 4 protected carbon tetrachloride-induced hepatic fibrosis in rats [18].…”

Maternal dietary omega-3 fatty acids and placental function

“…With regard to the placenta, in vitro administration of lipoxin A 4 (LXA 4 ) reduced LPSinduced apoptosis, pro-inflammatory cytokine secretion, and NFkB activity in human extravillous trophoblast cells, and in vivo administration of the synthetic LXA 4 analog, BML111, during mid-gestation reduced lowdose LPS-induced placental pro-inflammatory cytokine mRNA expression in rat (Lin et al 2012). Although these findings signify a potential for AA to promote pro-resolving effects via lipoxin generation, a balance must be met between these pro-resolving mediators and the potentially damaging effects of AA-derived proinflammatory eicosanoids.…”