Cited 29 time in webofscience Cited 35 time in scopus

Anti-inflammatory effects of genistein via suppression of the toll-like receptor 4-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglia

Title
Anti-inflammatory effects of genistein via suppression of the toll-like receptor 4-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglia
Authors
Jeong, JW[Jeong, Jin-Woo]Lee, HH[Lee, Hye Hyeon]Han, MH[Han, Min Ho]Kim, GY[Kim, Gi-Young]Kim, WJ[Kim, Wun-Jae]Choi, YH[Choi, Yung Hyun]
DGIST Authors
Jeong, JW[Jeong, Jin-Woo]
Issue Date
2014-04-05
Citation
Chemico: Biological Interactions, 212, 30-39
Type
Article
Article Type
Article
Keywords
Active Transport, Cell NucleusAnti-InflammationAnti-Inflammatory AgentsBV2 MicrogliaCell LineCell NucleusCyclooxygenase 2DinoprostoneDown-RegulationGenisteinInterleukin-1 BetaLipopolysaccharidesMicrogliaMyeloid Differentiation Factor 88NF-Kappa BNitric OxideNitric Oxide Synthase Type IiiSignal TransductionTLR4Toll-Like Receptor4Transcription Factor RelaTumor Necrosis Factor-Alpha
ISSN
0009-2797
Abstract
Genistein, a principal soy isoflavone, has received considerable attention as a protein kinase inhibitor. Although some studies have demonstrated that genistein possesses anti-inflammatory effects, the molecular mechanisms of genistein-mediated anti-inflammatory potential are unclear in microglial cells. In this study, we determined whether genistein attenuates pro-inflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia and attempted to establish the possible mechanisms. Our results indicated that genistein inhibited the production of nitric oxide (NO) and prostaglandin E2 at non-toxic concentrations by inhibiting inducible NO synthase and cyclooxygenase-2 expression. The increased release and expression of inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, by LPS, were markedly reduced by genistein. Genistein also attenuated LPS-induced reactive oxygen species generation and LPS-mediated nuclear translocation of nuclear factor-kappa B (NF-κB), associated with blocking degradation of the inhibitor of NF-κB-α. Furthermore, genistein potently suppressed binding of LPS to the microglial cell surface, indicating the antagonistic effect of genistein against toll like receptor 4 (TLR4), and inhibited LPS-induced TLR4 and myeloid differentiation factor 88 expression. In addition, blocking TLR4 signaling using the specific TLR4 signaling inhibitor CLI-095 increased the anti-inflammatory potential of genistein in BV2 microglia. Our data indicate that genistein may attenuate the initiation of intracellular signaling cascades by LPS through inhibiting NF-κB activation by inhibiting the binding of LPS to TLR-4 on microglial cells. ©2014 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/20.500.11750/2657
DOI
10.1016/j.cbi.2014.01.012
Publisher
ELSEVIER IRELAND LTD
Files:
There are no files associated with this item.
Collection:
Center for Core Research Facilities1. Journal Articles


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