Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice.

Maternal obesity is one of the major risk factors for pregnancy complications and is associated with low-grade chronic systemic inflammation due to higher levels of pro-inflammatory cytokines such as interleukin (IL)-1ß. Pregnant women with obesity have abnormal lipid profiles, characterized by higher levels of free fatty acids, especially palmitic acid (PA). Previously, we reported that PA stimulated IL-1ß secretion via activation of NLRP3 inflammasome in human placental cells. These observations led us to hypothesize that higher levels of PA induce NLRP3 inflammasome activation and placental inflammation, resulting in pregnancy complications. However, the effects of PA on NLRP3 inflammasome during pregnancy in vivo remain unclear. Therefore, PA solutions were administered intravenously into pregnant mice on day 12 of gestation. Maternal body weight was significantly decreased and absorption rates were significantly higher in PA-injected mice. The administration of PA significantly increased IL-1ß protein and the mRNA expression of NLRP3 inflammasome components (NLRP3, ASC, and caspase-1) within the placenta. In murine placental cell culture, PA significantly stimulated IL-1ß secretion, and this secretion was suppressed by a specific NLRP3 inhibitor (MCC950). Simultaneously, the number of macrophages/monocytes and neutrophils, together with the mRNA expression of these chemokines increased significantly in the placentas of PA-treated mice. Treatment with PA induced ASC assembling and IL-1ß secretion in macrophages, and this PA-induced IL-1ß secretion was significantly suppressed in NLRP3-knockdown macrophages. These results indicate that transient higher levels of PA exposure in pregnant mice activates NLRP3 inflammasome and induces placental inflammation, resulting in the incidence of absorption.

Olive Leaf Extract (OleaVita) Suppresses Inflammatory Cytokine Production and NLRP3 Inflammasomes in Human Placenta.

The placenta is essential for pregnancy and produces both pro-inflammatory and anti-inflammatory cytokines. Excessive production of inflammatory cytokines, involving interleukin-1ß (IL-1ß), IL-6, and IL-8, from placental tissues is associated with pregnancy complications. Olive leaf extract has several health benefits, including anti-inflammatory functions. OleaVita is a new commercial olive leaf extract; it is hypothesized to suppress placental inflammation. In human placental tissue culture, OleaVita treatment inhibited the secretion of inflammatory cytokines and NF-κB p65 protein expression. OleaVita also suppressed toll-like receptor ligands-induced IL-1ß secretion in human placental tissues. IL-1ß is regulated by the NLRP3 inflammasomes, a pivotal regulator of various diseases. OleaVita significantly decreased NLRP3 and pro-IL-1ß protein expression, suggesting that it has an inhibitory effect on NLRP3 inflammasome activation. Thus, OleaVita is beneficial as an inhibitor of inflammation and NLRP3 inflammasome activation, and may be used as a supplement for the treatment and prevention of inflammatory diseases.