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Anti-inflammatory effects of genistein via suppression of the toll-like receptor 4-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglia
- Anti-inflammatory effects of genistein via suppression of the toll-like receptor 4-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglia
- 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
- Chemico: Biological Interactions, 212, 30-39
- Article Type
- Active Transport, Cell Nucleus; Anti-Inflammation; Anti-Inflammatory Agents; BV2 Microglia; Cell Line; Cell Nucleus; Cyclooxygenase 2; Dinoprostone; Down-Regulation; Genistein; Interleukin-1 Beta; Lipopolysaccharides; Microglia; Myeloid Differentiation Factor 88; NF-Kappa B; Nitric Oxide; Nitric Oxide Synthase Type Iii; Signal Transduction; TLR4; Toll-Like Receptor4; Transcription Factor Rela; Tumor Necrosis Factor-Alpha
- 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.
- ELSEVIER IRELAND LTD
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