Oxytocin Modulates Microglial IL-17-Linked Inflammatory Pathways Through the IL-6/COX-2

Background: Neonatal neuroinflammation, driven by microglial activation and cytokine signaling, contributes to brain injury and adverse neurodevelopment outcomes. Perinatal inflammatory mediators, including IL-6, COX-2, and IL-17, prime microglia and influence circuit vulnerability. This study investigated whether oxytocin (OT) pretreatment attenuates lipopolysaccharide (LPS)-induced inflammatory priming in BV-2 microglial cells. Methods: BV-2 microglia were preincubated with OT (33ng/mL) for 2 hours, followed by LPS (0.5 µg/mL) for 2 hours. Expression of IBA1, a microglia marker, in BV-2 was assessed by immunofluorescence. After LPS treatment, the gene expression of BV-2 cells was assayed 2 and 6 hours post-LPS stimulation by RT-qPCR and RNA-seq. Functional characterization of gene expression profile was performed with KEGG and GO analyses. Results: Analyses of gene expression profile of BV-2 cells by RT-qPCR and RNA-seq revealed that OT pretreatment attenuated LPS-induced transcriptional activation, including IL-6 and COX-2 upregulation. KEGG pathway enrichment analyses suggested that OT-responsive genes were linked to the IL-17 signaling pathway. GO analyses showed enrichment for genes related to cytokine production, membrane raft, and chemokine activity. Conclusions: OT pretreatment mitigates LPS-induced microglial activation by modulating the IL-17–IL-6/COX-2 axis, suggesting its potential role for OT as an endogenous modulator of neuroinflammation during early brain development.