Elevated S100A9 in preeclampsia induces soluble endoglin and IL-1β secretion and hypertension via the NLRP3 inflammasome.

Abstract

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.

• Authors: Ayae Ozeki, Yuka Oogaki, Yuka Henmi, Tadayoshi Karasawa, Masafumi Takahashi, Hironori Takahashi, Akihide Ohkuchi, Koumei Shirasuna
• Journal: Journal of hypertension (J Hypertens) Vol. 40 Issue 1 Pg. 84-93 (01 01 2022) ISSN: 1473-5598 [Electronic] Netherlands
• PMID: 34412079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Calgranulin B
• Endoglin
• Inflammasomes
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• S100A9 protein, human
• S100A9 protein, mouse

Topics

• Animals
• Calgranulin B
• Endoglin
• Female
• Human Umbilical Vein Endothelial Cells (metabolism)
• Humans
• Hypertension
• Inflammasomes (metabolism)
• Interleukin-1beta (metabolism)
• Mice
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Placenta (metabolism)
• Pre-Eclampsia
• Pregnancy