title: Epigallocatechin gallate attenuates amyloid β-induced inflammation and neurotoxicity in EOC 13.31 microglia.
abstract: Microglia are the primary immune cells that contribute to neuroinflammation by releasing various proinflammatory cytokines and neurotoxins in the brain. Microglia-mediated neuroinflammation is one of the key characteristics of Alzheimer's disease (AD). Therefore, inhibitory reagents that prevent microglial activation may be used as potential therapeutic agents for treating AD. Recently, many studies have been performed to determine the bioactivities of green tea polyphenol epigallocatechin-3-gallate (EGCG), an efficient antioxidant that prevents neuroinflammation. However, limited information is available on the effects of EGCG on microglia-mediated neuroinflammation. In this study, we investigated the inhibitory effects of EGCG on amyloid β (Aβ)-induced microglial activation and neurotoxicity. Our results indicated that EGCG significantly suppressed the expression of tumor necrosis factor α (TNFα), interleukin-1β, interleukin-6, and inducible nitric oxide synthase (iNOS) in Aβ-stimulated EOC 13.31 microglia. EGCG also restored the levels of intracellular antioxidants nuclear erythroid-2 related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), thus inhibiting reactive oxygen species-induced nuclear factor-κB (NF-κB) activation after Aβ treatment. Furthermore, EGCG effectively protected neuro-2a neuronal cells from Aβ-mediated, microglia-induced cytotoxicity by inhibiting mitogen-activated protein kinase-dependent, Aβ-induced release of TNFα. Taken together, our findings suggested that EGCG suppressed Aβ-induced neuroinflammatory response of microglia and protected against indirect neurotoxicity. These results suggest that EGCG is a possible therapeutic agent for preventing Aβ-induced inflammatory neurodegeneration.
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Integrative Medicine, China Medical University, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: James
authors.initials: J
authors.lastname: Cheng-Chung Wei
authors.affiliation: Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
authors.forename: Hsiu-Chen
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Huang
authors.affiliation: Division of Basic Medical Science, Hungkuang University, Taichung, Taiwan.
authors.forename: Chiung-Huei
authors.initials: CH
authors.lastname: Peng
authors.affiliation: Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chih-Li
authors.initials: CL
authors.lastname: Lin
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D053583:Interleukin-1beta; D015850:Interleukin-6; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009498:Neurotoxins; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Amyloid β; Epigallocatechin gallate; Microglia; Neuroinflammation; Tumor necrosis factor α