OBJECTIVES: Maternal systemic and placental inflammatory responses participate 
in the pathogenesis of hypertensive disorders of pregnancy including 
preeclampsia, a pregnancy-specific syndrome, although the role of inflammation 
remains unclear. The NLRP3 inflammasome has been implicated in the control of 
sterile inflammation involved in preeclampsia. In the present study, we 
hypothesized that S100A9, as major alarmin, are associated with the pathogenesis 
of preeclampsia and induction of a preeclampsia-like phenotype in pregnant mice.
METHODS: Plasma were taken from normal pregnant women and preeclampsia patients. 
Human placental tissues, trophoblast cell line Sw.71 cells, and human umbilical 
vein endothelial cells (HUVEC) were treated with S100A9 with or without 
inhibitors associated with NLRP3 inflammasome. Pregnant mice were administered 
S100A9.
RESULTS: S100A9 was elevated in plasma and released from placentas of 
preeclampsia patients. S100A9 activated the NLRP3 inflammasome, resulting in 
IL-1β secretion, by human placental tissues and trophoblasts. In addition, 
secretion of soluble endoglin, a main contributor to the pathogenesis of 
preeclampsia, is regulated via S100A9-stimulated NLRP3 inflammasome activation 
in the human placenta and HUVECs. S100A9 administration significantly elevated 
maternal blood pressure and neutrophil accumulation within the placentas of 
pregnant mice, and both were significantly decreased in Nlrp3-knock out pregnant 
mice.
CONCLUSION: The results of this study demonstrated that S100A9 acts as a danger 
signal to activate the NLRP3 inflammasome in the placenta, associating with 
hypertension during pregnancy.