IL-1 beta but not the NALP3 inflammasome is an important determinant of endothelial cell responses to necrotic/dangerous trophoblastic debris

- Vascular endothelial cells constitutively express the NALP3 inflammasome.
- The NALP3 inflammasome in vascular endothelial cells can respond to specific danger signals including monosodium urate crystals.
- The NALP3 inflammasome is not responsible for the activation of vascular endothelial cells in response to necrotic trophoblastic debris.
- IL-1β derived from necrotic trophoblastic debris contributes to endothelial cell activation in response to the debris.
- The IL-1β derived from necrotic trophoblastic debris may contribute to maternal endothelial cell dysfunction in preeclampsia.

IntroductionNecrotic but not apoptotic trophoblastic debris can induce endothelial cell activation but the mechanism by which endothelial cells distinguish apoptotic from necrotic debris is unclear. The NALP3 inflammasome is a pattern recognition receptor that macrophages employ to recognise “danger signals” in necrotic cell corpses. In this study, we hypothesized that endothelial cells can identify and respond to necrotic trophoblastic debris via the NALP3 inflammasome.MethodsThe effect of trophoblastic debris on endothelial expression of NALP3 inflammasome components was investigated using qRT-PCR, immunoassays and fluorescent caspase 1 activity assay. IL-1β in was quantified by ELISA. Endothelial cell activation was measured by cell surface ICAM expression and monocytes adhesion assay.ResultsThe NALP3 inflammasome was expressed in resting vascular endothelial cells and is involved in endothelial response to danger signals. However, exposure to necrotic trophoblastic debris did not significantly alter the expression of any of the three components of the NALP3 inflammasome at the mRNA level, nor was caspase-1 activation increased. Conditioned media from endothelial cells exposed to necrotic trophoblastic debris contained elevated levels of IL-1β which was derived from the necrotic debris and which contributed to endothelial cell activation.DiscussionNecrotic trophoblastic debris induced endothelial cell activation through the IL-1β/IL-1R pathway. However, the NALP3 inflammasome in endothelial cells was not involved in this process.