title: Brevicompanine E reduces lipopolysaccharide-induced production of proinflammatory cytokines and enzymes in microglia by inhibiting activation of activator protein-1 and nuclear factor-kappaB.
abstract: Excessive release of proinflammatory cytokines by activated microglia can cause neurotoxicity in neurodegenerative diseases. We found that Brevicompanine E (BE), isolated from a deep ocean sediment derived fungus Penicillium sp., inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) production in microglia. Moreover, electrophoretic mobility shift assay (EMSA) demonstrated that BE attenuated nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) DNA binding activity in LPS-induced microglia. Consistent with this finding, BE inhibited LPS-induced IkappaBalpha degradation, NF-kappaB nuclear translocation, and also Akt, c-Jun NH2-terminal kinase (JNK) phosphorylation. Thus, BE may be potentially useful for modulating neuroinflammation.
authors.affiliation: Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Chonbuk, South Korea.
authors.forename: Xinying
authors.initials: X
authors.lastname: Yang
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.forename: Xuelian
authors.initials: X
authors.lastname: Tang
authors.forename: Suk-Yul
authors.initials: SY
authors.lastname: Jung
authors.forename: Bing
authors.initials: B
authors.lastname: Zheng
authors.forename: Byoung Yul
authors.initials: BY
authors.lastname: Soh
authors.forename: Sung-Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Qianqun
authors.initials: Q
authors.lastname: Gu
authors.forename: Hyun
authors.initials: H
authors.lastname: Park
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004268:DNA-Binding Proteins; D007211:Indoles; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010456:Peptides, Cyclic; D018808:Transcription Factor AP-1; C546178:brevicompanine E