Curcumin Attenuates gp120-Induced Microglial Inflammation by Inhibiting Autophagy via the PI3K Pathway

Area of Science:

• Neuroimmunology
• Cellular Biology
• Pharmacology

Background:

• Microglial inflammation is central to HIV-associated neurocognitive disorders.
• Curcumin has shown anti-inflammatory effects on microglia, but the mechanism is unclear.
• Autophagy, a cellular degradation process, can exacerbate inflammation when dysregulated.

Purpose of the Study:

• To investigate the role of autophagy in curcumin's anti-inflammatory effects on BV2 cells stimulated with gp120.
• To elucidate the signaling pathways involved in curcumin's action.

Main Methods:

• BV2 cells were treated with gp120, curcumin, and inhibitors of autophagy (3-MA) and key signaling molecules (NF-κB, IKK, AKT, PI3K).
• Inflammatory mediators (MCP-1, IL-17) were measured by ELISA.
• Autophagy markers (ATG5, LC3 II) and signaling pathway components were analyzed by Western Blot and nuclear translocation assays.
• Autophagic flux was visualized using mRFP-GFP-LC3 adenovirus.

Main Results:

• gp120 increased MCP-1 and IL-17 production, enhanced autophagic flux, and upregulated ATG5 and LC3 II expression.
• The autophagy inhibitor 3-MA reversed these gp120-induced effects.
• Curcumin mimicked 3-MA's effects, inhibiting NF-κB translocation and downregulating p-PI3K, p-AKT, and p-IKK.
• Curcumin suppressed gp120-induced BV2 cell inflammation by reducing autophagy via the PI3K/AKT/IKK/NF-κB pathway.

Conclusions:

• Curcumin attenuates gp120-induced microglial inflammation by inhibiting autophagy through the PI3K/AKT/IKK/NF-κB signaling pathway.
• This study clarifies the mechanism by which curcumin exerts its anti-inflammatory effects in the context of HIV neuroinflammation.
• Targeting autophagy and the PI3K/AKT/IKK/NF-κB pathway represents a potential therapeutic strategy for HIV-associated neurocognitive disorders.