Oxycodone alleviates LPS-induced neuroinflammation by regulating the CREB/miR-181c/PDCD4 axis

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• Neuroinflammation is a key factor in neurological diseases.
• Oxycodone exhibits anti-inflammatory effects.
• Microglia play a central role in neuroinflammation.

Purpose of the Study:

• To investigate oxycodone's effect on lipopolysaccharide (LPS)-induced neuroinflammation in microglia.
• To elucidate the molecular mechanisms underlying oxycodone's anti-inflammatory action.

Main Methods:

• HMC3 microglia cells were treated with LPS and varying concentrations of oxycodone.
• Gene and protein expression analyzed using qRT-PCR and Western blotting.
• Cytokine levels (TNF-α, IL-1β, IL-6, IL-8) measured by ELISA.
• Cell viability assessed via MTT assay.
• Molecular interactions explored using dual-luciferase reporter, ChIP, and RIP assays.

Main Results:

• Oxycodone treatment reduced LPS-induced inflammation and iNOS levels in HMC3 cells.
• Oxycodone increased p-CREB and miR-181c levels while decreasing PDCD4 expression.
• The CREB/miR-181c/PDCD4 axis was identified as the mechanism for oxycodone's anti-neuroinflammatory effect.

Conclusions:

• Oxycodone attenuates LPS-induced neuroinflammation in microglia by regulating the CREB/miR-181c/PDCD4 axis.
• Oxycodone demonstrates potential as a therapeutic agent for neuroinflammatory conditions.
• The study elucidates the specific molecular pathways involved in oxycodone's action.