PMID- 30155758 OWN - NLM STAT- MEDLINE DCOM- 20181217 LR - 20181217 IS - 1573-6830 (Electronic) IS - 0272-4340 (Linking) VI - 38 IP - 8 DP - 2018 Nov TI - Curcumin Attenuates gp120-Induced Microglial Inflammation by Inhibiting Autophagy via the PI3K Pathway. PG - 1465-1477 LID - 10.1007/s10571-018-0616-3 [doi] AB - 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-kappaB, 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-kappaB, 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-kappaB by preventing the translocation of NF-kappaB p65. Curcumin also inhibited the phosphorylation of p-PI3K, p-AKT, and p-IKK, which leads to down-regulation of NF-kappaB. Curcumin reduced autophagy via PI3K/AKT/IKK/NF-kappaB, thereby reducing BV2 cellular inflammation induced by gp120. FAU - Chen, Guiling AU - Chen G AD - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - Laboratory of Pathophysiology, State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, Guangdong, China. FAU - Liu, Sisi AU - Liu S AD - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - Laboratory of Pathophysiology, State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, Guangdong, China. FAU - Pan, Rui AU - Pan R AD - Department of Orthopaedics, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, Guangdong, China. FAU - Li, Guangming AU - Li G AD - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - Laboratory of Pathophysiology, State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, Guangdong, China. FAU - Tang, Haijie AU - Tang H AD - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - Laboratory of Pathophysiology, State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, Guangdong, China. FAU - Jiang, Mingliang AU - Jiang M AD - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - Laboratory of Pathophysiology, State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, Guangdong, China. FAU - Xing, Yanyan AU - Xing Y AD - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - Laboratory of Pathophysiology, State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, Guangdong, China. FAU - Jin, Fujun AU - Jin F AD - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - Laboratory of Pathophysiology, State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, Guangdong, China. FAU - Lin, Liqing AU - Lin L AD - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - Laboratory of Pathophysiology, State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. AD - GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, Guangdong, China. FAU - Dong, Jun AU - Dong J AD - Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. dongjunbox@163.com. AD - Laboratory of Pathophysiology, State Administration of Traditional Chinese Medicine, School of Medicine, Jinan University, Guangzhou, 510632, Guangdong, China. dongjunbox@163.com. AD - GHM Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, Guangdong, China. dongjunbox@163.com. LA - eng GR - 81171134/the National Natural Science Foundation of China/ GR - 81471235/the National Natural Science Foundation of China/ GR - 2014A030313360/Guangdong Provincial Natural Science Foundation of China/ GR - B14036/the Program of Introducing Talents of Discipline to Universities/ GR - 2010B030700016/the Science and Technology Foundation of Guangdong/ GR - No.21617460/the cultivation and innovation fund of Jinan University/ PT - Journal Article DEP - 20180828 PL - United States TA - Cell Mol Neurobiol JT - Cellular and molecular neurobiology JID - 8200709 RN - 0 (Chemokine CCL2) RN - 0 (HIV Envelope Protein gp120) RN - 0 (I-kappa B Proteins) RN - 0 (Interleukin-17) RN - 0 (NF-kappa B) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - IT942ZTH98 (Curcumin) SB - IM MH - Animals MH - Autophagosomes/drug effects/metabolism MH - Autophagy/*drug effects MH - Chemokine CCL2/metabolism MH - Curcumin/*pharmacology MH - HIV Envelope Protein gp120/*toxicity MH - I-kappa B Proteins/metabolism MH - Inflammation/*pathology MH - Interleukin-17/metabolism MH - Mice MH - Microglia/*pathology MH - NF-kappa B/metabolism MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - *Signal Transduction OTO - NOTNLM OT - Autophagy OT - Curcumin OT - Inflammation OT - Microglia OT - PI3K OT - gp120 EDAT- 2018/08/30 06:00 MHDA- 2018/12/18 06:00 CRDT- 2018/08/30 06:00 PHST- 2018/04/12 00:00 [received] PHST- 2018/08/22 00:00 [accepted] PHST- 2018/08/30 06:00 [pubmed] PHST- 2018/12/18 06:00 [medline] PHST- 2018/08/30 06:00 [entrez] AID - 10.1007/s10571-018-0616-3 [pii] AID - 10.1007/s10571-018-0616-3 [doi] PST - ppublish SO - Cell Mol Neurobiol. 2018 Nov;38(8):1465-1477. doi: 10.1007/s10571-018-0616-3. Epub 2018 Aug 28.