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

Area of Science:

• Neuroscience
• Immunology
• Developmental Biology

Background:

• Neonatal neuroinflammation, involving microglial activation and cytokine signaling, can cause brain injury and neurodevelopmental issues.
• Perinatal inflammatory mediators like interleukin-6 and cyclooxygenase-2 prime microglia, affecting brain circuit vulnerability.

Purpose of the Study:

• To investigate if oxytocin pretreatment can reduce lipopolysaccharide (LPS)-induced inflammatory priming in BV-2 microglial cells.
• To understand the molecular mechanisms by which oxytocin affects microglial inflammatory responses.

Main Methods:

• BV-2 microglial cells were pretreated with oxytocin, followed by LPS stimulation.
• Gene expression analysis was performed using RT-qPCR and RNA-seq at various time points post-stimulation.
• Immunofluorescence was used to assess the expression of the microglia marker ionized calcium-binding adapter molecule 1.

Main Results:

• Oxytocin pretreatment significantly attenuated LPS-induced upregulation of interleukin-6 and cyclooxygenase-2.
• RNA-seq analysis revealed that oxytocin-responsive genes are associated with the interleukin-17 signaling pathway.
• Gene Ontology analysis indicated enrichment for genes involved in cytokine production and chemokine activity.

Conclusions:

• Oxytocin pretreatment mitigates LPS-induced microglial activation by modulating the interleukin-17/interleukin-6/cyclooxygenase-2 axis.
• Oxytocin shows potential as an endogenous modulator of neuroinflammation in early brain development.