title: Green tea epigallocatechin-3-gallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune encephalomyelitis.
abstract: Recent studies in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE), point to the fact that even in the early phase of inflammation, neuronal pathology plays a pivotal role in the sustained disability of affected individuals. We show that the major green tea constituent, (-)-epigallocatechin-3-gallate (EGCG), dramatically suppresses EAE induced by proteolipid protein 139-151. EGCG reduced clinical severity when given at initiation or after the onset of EAE by both limiting brain inflammation and reducing neuronal damage. In orally treated mice, we found abrogated proliferation and TNF-alpha production of encephalitogenic T cells. In human myelin-specific CD4+ T cells, cell cycle arrest was induced, down-regulating the cyclin-dependent kinase 4. Interference with both T cell growth and effector function was mediated by blockade of the catalytic activities of the 20S/26S proteasome complex, resulting in intracellular accumulation of IkappaB-alpha and subsequent inhibition of NF-kappaB activation. Because its structure implicates additional antioxidative properties, EGCG was capable of protecting against neuronal injury in living brain tissue induced by N-methyl-D-aspartate or TRAIL and of directly blocking the formation of neurotoxic reactive oxygen species in neurons. Thus, a natural green tea constituent may open up a new therapeutic avenue for young disabled adults with inflammatory brain disease by combining, on one hand, anti-inflammatory and, on the other hand, neuroprotective capacities.
authors.affiliation: Institute of Neuroimmunology, Neuroscience Research Center, Charité, Berlin, Germany.
authors.forename: Orhan
authors.initials: O
authors.lastname: Aktas
authors.forename: Timour
authors.initials: T
authors.lastname: Prozorovski
authors.forename: Alina
authors.initials: A
authors.lastname: Smorodchenko
authors.forename: Nicolai E
authors.initials: NE
authors.lastname: Savaskan
authors.forename: Roland
authors.initials: R
authors.lastname: Lauster
authors.forename: Peter-Michael
authors.initials: PM
authors.lastname: Kloetzel
authors.forename: Carmen
authors.initials: C
authors.lastname: Infante-Duarte
authors.forename: Stefan
authors.initials: S
authors.lastname: Brocke
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D015536:Down-Regulation / Q000187:drug effects; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins / Q000096:biosynthesis; D007111:Immunity, Cellular / Q000187:drug effects; D019169:Jurkat Cells; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D013662:Tea; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D006131:Growth Inhibitors; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D018696:Neuroprotective Agents; C000606205:Nfkbia protein, mouse; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D013662:Tea; D000072000:NF-KappaB Inhibitor alpha; D002392:Catechin; C045651:epigallocatechin gallate; C495900:CDK4 protein, human; C495902:Cdk4 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases