title: Saturated fatty acids activate microglia via Toll-like receptor 4/NF-κB signalling.
abstract: Diets rich in SFA have been implicated in Alzheimer's disease (AD). There is strong evidence to suggest that microglial activation augments the progression of AD. However, it remains uncertain whether SFA can initiate microglial activation and whether this response can cause neuronal death. Using the BV-2 microglial cell line and primary microglial culture, we showed that palmitic acid (PA) and stearic acid (SA) could activate microglia, as assessed by reactive morphological changes and significantly increased secretion of pro-inflammatory cytokines, NO and reactive oxygen species, which trigger primary neuronal death. In addition, the mRNA level of these pro-inflammatory mediators determined by RT-PCR was also increased by PA and SA. We further investigated the intracellular signalling mechanism underlying the release of pro-inflammatory mediators from PA-activated microglial cells. The present results showed that PA activated the phosphorylation and nuclear translocation of the p65 subunit of NF-κB. Furthermore, pyrrolidine dithiocarbamate, a NF-κB inhibitor, attenuated the production of pro-inflammatory mediators except for IL-6 in PA-stimulated microglia. Administration of anti-Toll-like receptor (TLR)4-neutralising antibody repressed PA-induced NF-κB activation and pro-inflammatory mediator production. In conclusion, the present in vitro study demonstrates that SFA could activate microglia and stimulate the TLR4/NF-κB pathway to trigger the production of pro-inflammatory mediators, which may contribute to neuronal death.
authors: Shandong Provincial Key Laboratory of Mental Disorders, Department of Histology and Embryology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong 250012, People's Repubic of China.
authors: Zhen
authors: Z
authors: Wang
authors: Dexiang
authors: D
authors: Liu
authors: Fuwu
authors: F
authors: Wang
authors: Shangming
authors: S
authors: Liu
authors: Shidou
authors: S
authors: Zhao
authors: Eng-Ang
authors: EA
authors: Ling
authors: Aijun
authors: A
authors: Hao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D019308:Palmitic Acid / Q000009:adverse effects*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013229:Stearic Acids / Q000009:adverse effects*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C498144:Rela protein, mouse; D013229:Stearic Acids; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D019308:Palmitic Acid; C031183:stearic acid; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse