Browsing by Subject "Preterm prelabor rupture of membranes"

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    Matrix metalloproteinases in preterm prelabor rupture of membranes in the setting of chorioamnionitis: A scoping review
    (Wiley, 2023) Nguyen, Lynsa M.; Aronoff, David M.; Eastman, Alison J.; Medicine, School of Medicine
    Fetal or gestational membranes extend from the placenta to enclose the fetus and amniotic fluid. While the membranes spontaneously rupture at term in normal pregnancies, they can rupture prematurely before the onset of labor, termed preterm prelabor rupture of membranes (PPROM). PPROM can be triggered by bacterial infection or sterile inflammation in the membranes, known as chorioamnionitis (CAM). The membranes derive their tensile strength from a collagen-rich extracellular matrix (ECM); as such, understanding the enzymes and processes that can degrade the membrane ECM are of paramount importance. Matrix metalloproteinases (MMPs) are a class of enzymes capable of degrading collagen and other components of the ECM, and can be induced by inflammation. We used a scoping review to address the question of how MMP activity is associated with PPROM, particularly their induction due to sterile or nonsterile CAM. We have found that the most studied MMPs in PPROM were MMPs 2, 8, and 9. Additionally, some MMPs are constitutively active, while others are induced by inflammation. Mechanistic studies of the pathways that induce MMP activation are sparse, and this area is ripe for future studies. Targeting MMP activation could be a future strategy to delay or prevent PPROM.
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    Palmitate and group B Streptococcus synergistically and differentially induce IL-1β from human gestational membranes
    (Frontiers Media, 2024-05-23) Gaddy, Jennifer A.; Moore, Rebecca E.; Lochner, Jonathan S.; Rogers, Lisa M.; Noble, Kristen N.; Giri, Ayush; Aronoff, David M.; Cliffel, David; Eastman, Alison J.; Medicine, School of Medicine
    Introduction: Rupture of the gestational membranes often precedes major pregnancy complications, including preterm labor and preterm birth. One major cause of inflammation in the gestational membranes, chorioamnionitis (CAM) is often a result of bacterial infection. The commensal bacterium Streptococcus agalactiae, or Group B Streptococcus (GBS) is a leading infectious cause of CAM. Obesity is on the rise worldwide and roughly 1 in 4 pregnancy complications is related to obesity, and individuals with obesity are also more likely to be colonized by GBS. The gestational membranes are comprised of several distinct cell layers which are, from outermost to innermost: maternally-derived decidual stromal cells (DSCs), fetal cytotrophoblasts (CTBs), fetal mesenchymal cells, and fetal amnion epithelial cells (AECs). In addition, the gestational membranes have several immune cell populations; macrophages are the most common phagocyte. Here we characterize the effects of palmitate, the most common long-chain saturated fatty acid, on the inflammatory response of each layer of the gestational membranes when infected with GBS, using human cell lines and primary human tissue. Results: Palmitate itself slightly but significantly augments GBS proliferation. Palmitate and GBS co-stimulation synergized to induce many inflammatory proteins and cytokines, particularly IL-1β and matrix metalloproteinase 9 from DSCs, CTBs, and macrophages, but not from AECs. Many of these findings are recapitulated when treating cells with palmitate and a TLR2 or TLR4 agonist, suggesting broad applicability of palmitate-pathogen synergy. Co-culture of macrophages with DSCs or CTBs, upon co-stimulation with GBS and palmitate, resulted in increased inflammatory responses, contrary to previous work in the absence of palmitate. In whole gestational membrane biopsies, the amnion layer appeared to dampen immune responses from the DSC and CTB layers (the choriodecidua) to GBS and palmitate co-stimulation. Addition of the monounsaturated fatty acid oleate, the most abundant monounsaturated fatty acid in circulation, dampened the proinflammatory effect of palmitate. Discussion: These studies reveal a complex interplay between the immunological response of the distinct layers of the gestational membrane to GBS infection and that such responses can be altered by exposure to long-chain saturated fatty acids. These data provide insight into how metabolic syndromes such as obesity might contribute to an increased risk for GBS disease during pregnancy.