Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis

Area of Science:

• Obstetrics and Gynecology
• Immunology
• Pharmacology

Background:

• Chorioamnionitis (CAM) is a major cause of adverse pregnancy outcomes, including preterm birth and neonatal sepsis.
• Formyl peptide receptor 2 (FPR2), a G protein-coupled receptor, is implicated in inflammatory diseases and found in the human placenta.
• Resolvin D1 (RvD1) is known to resolve inflammation via FPR2 interactions.

Purpose of the Study:

• To investigate the role and therapeutic potential of FPR2 and RvD1 in chorioamnionitis.
• To elucidate the underlying molecular mechanisms involving the FPR2/PPARγ/NF-κB pathway in CAM.

Main Methods:

• Analysis of FPR2 expression in human placental tissues from CAM patients.
• Utilizing formyl peptide receptor 2 knockout (Fpr2-/-) and wild-type (WT) mice in LPS-induced CAM models.
• In vitro studies using a trophoblast inflammation model.
• Assessment of RvD1's effects on inflammation and preterm labor in mouse models.

Main Results:

• FPR2 expression was elevated in placentas from CAM patients, with corresponding changes in PPARγ/NF-κB signaling.
• Fpr2-/- mice exhibited increased susceptibility to LPS and exacerbated CAM symptoms compared to WT mice.
• RvD1 treatment mitigated LPS-induced inflammation in vitro and in vivo by engaging FPR2 and its downstream pathway.
• RvD1 administration improved preterm labor outcomes in a mouse model of LPS-induced CAM.

Conclusions:

• RvD1 effectively alleviates trophoblast inflammation in both in vitro and in vivo models of CAM.
• The therapeutic effects of RvD1 in CAM are mediated through the FPR2/PPARγ/NF-κB pathway.
• The RvD1/FPR2 axis presents a promising novel therapeutic strategy for managing chorioamnionitis.