Brevicompanine E reduces lipopolysaccharide-induced production of proinflammatory cytokines and enzymes in microglia by inhibiting activation of activator protein-1 and nuclear factor-kappaB.
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.
Yang
Xinying
X
Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Chonbuk, South Korea.
Du
Lin
L
Tang
Xuelian
X
Jung
Suk-Yul
SY
Zheng
Bing
B
Soh
Byoung Yul
BY
Kim
Sung-Yeon
SY
Gu
Qianqun
Q
Park
Hyun
H
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
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