title: Anti-inflammatory effects of lipoic acid through inhibition of GSK-3β in lipopolysaccharide-induced BV-2 microglial cells.
abstract: Activated microglial cells play an important role in immune and inflammatory responses in CNS and play a role in neurodegenerative diseases. We examined the effects of lipoic acid (LA) on inflammatory responses of BV-2 microglial cells activated by lipopolysaccharide (LPS), and explored the underlying mechanisms of action of LA. BV-2 cells treated with LPS showed an up-regulation of mRNA of the pro-inflammatory molecules, inducible nitric oxide synthase (iNOS). LA suppressed the expression of iNOS and furthermore, LPS-induced production of nitrite. Moreover, LA suppressed the nuclear translocation of RelA, a component of nuclear factor-kappa B (NF-κB) that contains transcriptional activator domain for LPS. The mechanisms of LA-mediated anti-inflammatory effects on microglia remain unknown, and we suggested an involvement of Akt/glycogen synthase kinase-3β (GSK-3β) phosphorylation. The results showed that inhibitor of phosphatidylinositol 3-kinase prevented LA-mediated suppression of LPS induction of RelA and expression of iNOS. Furthermore, these inflammatory actions were prevented by GSK-3β inhibitors. These data demonstrate a role for LA as a chemical modulator of inflammatory responses by microglia, and thus may be a therapeutic strategy for treating neurodegenerative diseases with an inflammatory component.
authors.affiliation: Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8640, Japan. Electronic address: koriyama@med.kanazawa-u.ac.jp.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Koriyama
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nakayama
authors.forename: Seiichi
authors.initials: S
authors.lastname: Matsugo
authors.forename: Kayo
authors.initials: K
authors.lastname: Sugitani
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ogai
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Takadera
authors.forename: Satoru
authors.initials: S
authors.lastname: Kato
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008070:Lipopolysaccharides / Q000494:pharmacology; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D051996:Transcription Factor RelA; D008063:Thioctic Acid; D052247:Nitric Oxide Synthase Type II; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride
keywords: Akt; GSK-3β; IL-1β; Inflammation; LA; LPS; LY; LY294002; LiCl; Lipoic acid; Microglia; NF-κB; TNFα; glycogen synthase kinase-3β; iNOS; inducible nitric oxide synthase; interleukin-1β; lipoic acid; lipopolysaccharide; lithium chloride; nuclear factor-kappa B; tumor necrosis factor α