Abstract
Microglial inflammation plays an essential role in the pathogenesis of HIV-associated neurocognitive disorders. A previous study indicated that curcumin relieved microglial inflammatory responses. However, the mechanism of this process remained unclear. Autophagy is a lysosome-mediated cell content-dependent degradation pathway, and uncontrolled autophagy leads to enhanced inflammation. The role of autophagy in curcumin-attenuating BV2 cell inflammation caused by gp120 was investigated with or without pretreatment with the autophagy inhibitor 3-MA and blockers of NF-κB, IKK, AKT, and PI3K, and we then detected the production of the inflammatory mediators monocyte chemoattractant protein-1 (MCP-1) and IL17 using ELISA, and autophagy markers ATG5 and LC3 II by Western Blot. The autophagic flux was observed by transuding mRFP-GFP-LC3 adenovirus. The effect of the blockers on gp120-induced BV2 cells was examined by the expression of p-AKT, p-IKK, NF-κB, and p65 in the nuclei and LC3 II and ATG5. gp120 promoted the expression of MCP-1 and IL-17, enhanced autophagic flux, and up-regulated the expression of LC3 II and ATG5, while the autophagy inhibitor 3-MA down-regulated the phenomena above. Curcumin has similar effects with 3-MA, in which curcumin inhibited NF-κB by preventing the translocation of NF-κB p65. Curcumin also inhibited the phosphorylation of p-PI3K, p-AKT, and p-IKK, which leads to down-regulation of NF-κB. Curcumin reduced autophagy via PI3K/AKT/IKK/NF-κB, thereby reducing BV2 cellular inflammation induced by gp120.