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• W2032875315 abstract "Intrauterine infection is a common trigger for preterm birth and is also a risk factor for the subsequent development of neurodevelopmental abnormalities in the neonate. Bacterial lipopolysaccharide (LPS) binds to toll-like receptor-4 (TLR-4) to activate proinflammatory signaling pathways, which are implicated in both preterm delivery and antenatal brain injury. The transcription factor nuclear factor-κB (NF-κB) is a key player in the orchestration of the inflammatory response and has a central role in parturition. Here we show that intrauterine administration of TLR-4-specific LPS to pregnant mice results in the activation of NF-κB in the maternal uterus and the fetal brain, up-regulation of proinflammatory proteins cyclooxygenase-2, chemokine ligand 1, ChemoKine (C-C motif) ligand 2, and cytosolic phospholipase A2 in myometrium, and induction of preterm delivery. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an antiinflammatory prostaglandin that plays a role in promoting the resolution of inflammation. We report that coadministration of 15d-PGJ2 and LPS to pregnant mice delays LPS-induced preterm delivery and confers protection from LPS-induced fetal mortality. This is associated with inhibition of myometrial NF-κB, cytosolic phospholipase A2, and c-Jun N-terminal kinase activation, and of inflammatory protein synthesis. Therefore 15d-PGJ2 has anti-inflammatory effects via inhibition of multiple aspects of inflammation-driven TRL-4 signaling pathway. Thus, 15d-PGJ2 or compounds with similar antiinflammatory functions may have potential as therapeutic agents in the management of preterm labor with the added advantage of preventing detrimental effects to the fetus that may result from infection/inflammation. Intrauterine lipopolysaccharide administration to pregnant mice activates nuclear factor-κ and Jun N-terminal kinase, causing preterm labor. 15-deoxy-Δ12,14-prostaglandin J2 inhibits this via multiple aspects of the toll-like receptor-4 signaling pathway." @default.
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• W2032875315 date "2009-02-01" @default.
• W2032875315 modified "2023-09-24" @default.
• W2032875315 title "The Cyclopentenone 15-Deoxy-Δ12,14-Prostaglandin J2 Delays Lipopolysaccharide-Induced Preterm Delivery and Reduces Mortality in the Newborn Mouse" @default.
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• W2032875315 doi "https://doi.org/10.1210/en.2008-1178" @default.
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