Peripheral Blood Mononuclear Cells Infiltration Downregulates Decidual FAAH Activity in an LPS‐Induced Embryo Resorption Model

Abstract

Maternal infections with gram-negative bacteria are associated with miscarriage and are one of the most common complications during pregnancy. Previous studies from our group have shown that lipopolysaccharide (LPS)-activated infiltrating peripheral blood mononuclear cells (PBMC) into decidual tissue plays an important role in the establishment of a local inflammatory process that results in embryo cytotoxicity and early embryo resorption. Moreover, we have also shown that an increased endocannabinoid tone mediates LPS-induced deleterious effects during early pregnancy loss. Here, we sought to investigate whether the infiltrating PBMC modulates the decidual endocannabinoid tone and the molecular mechanisms involved. PBMC isolated from 7-day pregnant mice subjected to different treatments were co-cultured in a transwell system with decidual tissue from control 7-day pregnant mice. Decidual fatty acid amide hydrolase (FAAH) activity was measured by radioconvertion, total decidual protein nitration by Western blot (WB), and decidual FAAH nitration by immunoprecipitation followed by WB. We found that co-culture of PBMC obtained from LPS-treated mice increased the level of nitration of decidual FAAH, which resulted in a negative modulation of decidual FAAH activity. Interestingly, co-treatment with progesterone or aminoguanidine prevented this effect. We found that LPS-treated PBMC release high amounts of nitric oxide (NO) which causes tyrosine nitration of decidual FAAH, diminishing its enzymatic activity. Inactivation of FAAH, the main degrading enzyme of anandamide and similar endocannabinoids, could lead to an increased decidual endocannabinoid tone with embryotoxic effects. J. Cell. Physiol. 232: 1441-1447, 2017. © 2016 Wiley Periodicals, Inc.

Genistein promotes M1 macrophage apoptosis and reduces inflammatory response by disrupting miR-21/TIPE2 pathway

“…Drug treatment was determined by referencing previous studies ( Kim et al, 2011 , Cong et al, 2021a , Cong et al, 2021b , Xie et al, 2021a , Xie et al, 2021b ). After 20 weeks, the mice were sacrificed by cervical dislocation and peripheral blood mononuclear cells (PBMCs), aortas and peritoneal macrophages (PMφs) were harvested ( Wolfson et al, 2017 , Xie et al, 2021a , Xie et al, 2021b ). All procedures strictly agreed with National Institutes of Health guidelines for care and use of laboratory animals and were approved by Ethics Committee of Hunan Normal University.…”

Promising benefit of resveratrol in preventing preterm birth: A systematic review

“…Studies conducted on mouse models, specifically those with spontaneous and inflammation-induced PTB with p53 deletion (p53 d/d females), have indicated the involvement of mTOR activation in decidual senescence and the excessive production of PGs derived from COX2, ultimately leading to PTB (11). In female mice with the p53 d/d phenotype, a noticeable decrease in the growth of uterine decidual cells due to accelerated senescence has been observed (92,93). This condition is accompanied by elevated levels of pAkt, p21, IL-8 and various CXCL cytokines, collectively contributing to the senescence-associated secretory phenotype, which further promotes decidual senescence and PTB (93).…”

“…In female mice with the p53 d/d phenotype, a noticeable decrease in the growth of uterine decidual cells due to accelerated senescence has been observed (92,93). This condition is accompanied by elevated levels of pAkt, p21, IL-8 and various CXCL cytokines, collectively contributing to the senescence-associated secretory phenotype, which further promotes decidual senescence and PTB (93). Additionally, this p53 deletion has been associated with PTB, which can also be influenced by factors, such as increased ROS production due to conditions such as pre-eclampsia, as well as environmental factors such as smoking and pollution (93).…”