title: Transcription factor Nrf2 suppresses LPS-induced hyperactivation of BV-2 microglial cells.
abstract: Microglial hyperactivation is a hallmark of neurodegenerative diseases and the suppression of microglial hyperactivation is being investigated as a means to treat inflammation-mediated neurodegenerative disorders. Here we report that transcription factor Nrf2 in BV-2 microglia, which regulates the expression of phase II antioxidant enzyme genes, decreased the levels of LPS-induced inflammatory cytokines and mediators. These anti-inflammatory effects were not due to Nrf2-mediated up-regulation of phase II enzymes, since over-expression of these enzymes failed to suppress LPS-mediated microglial hyperactivation. However, Nrf2 inhibited LPS-derived increases in p38 MAPK phosphorylation and NF-κB activation. This suggests that Nrf2 inhibits microglial hyperactivation by suppressing p38 MAPK and NF-κB signaling pathway.
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Kyungmi
authors.initials: K
authors.lastname: Koh
authors.forename: Jaekyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jang
authors.forename: Keejung
authors.initials: K
authors.lastname: Yoon
authors.forename: Youngnam
authors.initials: Y
authors.lastname: Cha
authors.forename: Hyong Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005911:Gliosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases