Inhibitory effect of a tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl)-2-butenal on amyloid-β generation and inflammatory reactions via inhibition of NF-κB and STAT3 activation in cultured astrocytes and microglial BV-2 cells

Journal of Neuroinflammation

Jin Tae Hong²  Ki-Wan Oh¹  Sang Bae Han²  Heon-Sang Jeong³  Jin-Yi Han¹  Im Seup Choi²  Dong-Young Choi²  Young-Jung Lee² 

[1] College of Pharmacy, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea;CBITRC, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea;College of Agriculture, Life and Environments Sciences, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea

关键词: amyloidogenesis;    neuroinflammation;    STAT3;    NF-κB;    2,4-bis(p-hydroxyphenyl)-2-butenal;   

Others  :  1213081
DOI  :  10.1186/1742-2094-8-132

 received in 2011-03-13, accepted in 2011-10-07,  发布年份 2011

【 摘 要 】

Background

Amyloidogenesis is linked to neuroinflammation. The tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl)-2-butenal, possesses anti-inflammatory properties in cultured macrophages, and in an arthritis animal model. Because astrocytes and microglia are responsible for amyloidogenesis and inflammatory reactions in the brain, we investigated the anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl)-2-butenal in lipopolysaccharide (LPS)-stimulated astrocytes and microglial BV-2 cells.

Methods

Cultured astrocytes and microglial BV-2 cells were treated with LPS (1 μg/ml) for 24 h, in the presence (1, 2, 5 μM) or absence of 2,4-bis(p-hydroxyphenyl)-2-butenal, and harvested. We performed molecular biological analyses to determine the levels of inflammatory and amyloid-related proteins and molecules, cytokines, Aβ, and secretases activity. Nuclear factor-kappa B (NF-κB) DNA binding activity was determined using gel mobility shift assays.

Results

We found that 2,4-bis(p-hydroxyphenyl)-2-butenal (1, 2, 5 μM) suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in LPS (1 μg/ml)-stimulated astrocytes and microglial BV-2 cells. Further, 2,4-bis(p-hydroxyphenyl)-2-butenal inhibited the transcriptional and DNA binding activity of NF-κB--a transcription factor that regulates genes involved in neuroinflammation and amyloidogenesis via inhibition of IκB degradation as well as nuclear translocation of p50 and p65. Consistent with the inhibitory effect on inflammatory reactions, 2,4-bis(p-hydroxyphenyl)-2-butenal inhibited LPS-elevated Aβ₄₂ levels through attenuation of β- and γ-secretase activities. Moreover, studies using signal transducer and activator of transcription 3 (STAT3) siRNA and a pharmacological inhibitor showed that 2,4-bis(p-hydroxyphenyl)-2-butenal inhibits LPS-induced activation of STAT3.

Conclusions

These results indicate that 2,4-bis(p-hydroxyphenyl)-2-butenal inhibits neuroinflammatory reactions and amyloidogenesis through inhibition of NF-κB and STAT3 activation, and suggest that 2,4-bis(p-hydroxyphenyl)-2-butenal may be useful for the treatment of neuroinflammatory diseases like Alzheimer's disease.

【 授权许可】

   
2011 Lee et al; licensee BioMed Central Ltd.

【 图 表 】

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