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.
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Abbreviations
- HAND:
-
HIV-associated neurocognitive disorders
- Cur:
-
Curcumin
- MCP-1:
-
Monocyte chemoattractant protein-1
- LC3:
-
Light chain 3
- ATG5:
-
Autophagy-related gene 5
- PI3K:
-
Phosphatidylinositol 3 kinase
- AKT:
-
Protein kinase B
- IKK:
-
IκB kinase
- NF-κB:
-
Nuclear transcription factor-κB
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (81171134 and 81471235), Guangdong Provincial Natural Science Foundation of China (2014A030313360), the Program of Introducing Talents of Discipline to Universities (B14036), the Science and Technology Foundation of Guangdong (2010B030700016), and the cultivation and innovation fund of Jinan University (No. 21617460).
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JD designed the study. GC, SL, and RP performed the studies. MJ and LL assisted in part of the experiment. GL and HT analysed the data and interpreted the results. GC and JD wrote the paper. YX and FJ edited the paper. All authors read and approved the final manuscript.
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The authors declare no conflicts of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.
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Chen, G., Liu, S., Pan, R. et al. Curcumin Attenuates gp120-Induced Microglial Inflammation by Inhibiting Autophagy via the PI3K Pathway. Cell Mol Neurobiol 38, 1465–1477 (2018). https://doi.org/10.1007/s10571-018-0616-3
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DOI: https://doi.org/10.1007/s10571-018-0616-3