OP 28 Inflammation in preeclampsia by nod-like receptor protein (nlrp)3 inflammasome activation in trophoblasts

Introduction Preeclampsia (PE) is characterized by an aberrant inflammatory response to pregnancy. A stressed and inflamed placenta will induce maternal systemic inflammation, leading to hypertension with proteinuria (i.e. PE). The harmful placental inflammation involves abnormal placental expression of danger-sensing pattern recognition receptors (PRRs). Increased maternal cholesterol and uric acid levels are also associated with PE development. Crystalline cholesterol and uric acid may activate the PRR named nod-like receptor protein (NLRP)3 inflammasome to release the potent inflammatory cytokine IL-1 β , resulting in vigorous inflammation. Objective We aimed to characterize crystal-induced NLRP3 activation in placental inflammation, and examine its role in PE development. Materials and methods Total cholesterol, uric acid, soluble fms-like tyrosine kinase-1 (sFlt-1) and high sensitivity C-reactive protein (hsCRP) were measured in serum from pregnant women with ( n  = 34) or without ( n  = 43) PE and non-pregnant women ( n  = 28). Specific cell markers, central NLRP3 inflammasome pathway components (NLRP3, caspase 1 and IL-1 β ) , and complement factors (C5a and TCC) were detected by immunohistochemistry in third trimester placental samples from healthy ( n  = 13) and PE pregnancies ( n  = 23). Placental explants and the trophoblast cell line SGHPL-5 were primed with lipopolysaccharide (LPS) or C5a/tumor necrosis factor (TNF)- α and stimulated with cholesterol or uric acid crystals. Resulting IL-1 β response was quantified by ELISA. Results Cholesterol and uric acid levels were elevated in maternal serum from PE compared to healthy pregnancies and correlated with levels of hsCRP and sFlt-1. The NLRP3 inflammasome components and complement factors were expressed by placental syncytiotrophoblast (SCT), and the IL-1 β and TCC expression in SCT was significantly higher in PE compared to healthy pregnancies. C5a positive regions of the SCT were observed more frequently in PE placentas. Complement primed crystal stimulation induced NLRP3 dependent IL-1 β production in trophoblasts and explants cultures.