Nuclear-targeted inhibition of NF-κB on MMP-9 production by N-2-(4-bromophenyl) ethyl caffeamide in human monocytic cells

Yung Chen Chou, Joen Rong Sheu, Chi Li Chung, Chung Yung Chen, Fan Li Lin, Ming Jen Hsu, Yueh Hsiung Kuo, George Hsiao

研究成果: 雜誌貢獻文章

53 引文 斯高帕斯(Scopus)

摘要

Aberrant remodeling of the extracellular matrix occurs in many pathological processes, and its breakdown is mainly accomplished by matrix metalloproteinases (MMPs), which participate in the course of inflammation and tumor invasion. Nuclear factor-κB (NF-κB), a key transcription factor for the production of MMP-9, can be activated by various proinflammatory cytokines and promotes inflammation. In the present study, we investigated the intracellular mechanism for the inhibitory effects of an analogue of N-hydroxycinnamoylphenalkylamides, N-2-(4-bromophenyl) ethyl caffeamide (EK5), on tumor necrosis factor (TNF)-α stimulated expression of MMP-9 in a human monocytic cell line, THP-1. Our results show that TNF-α-induced expression of MMP-9 at both mRNA and protein levels was completely blocked by EK5 in a concentration-dependent (1-20 μM) manner. We also found that EK5 markedly suppressed NF-κB signaling as detected by the NF-κB reporter gene assay but had no effects on the degradation of IκBα or translocation of NF-κB. Interestingly, chromatin immunoprecipitation results revealed that the association between p65 and MMP-9 promoter gene was completely abrogated by EK5, but the p65 phosphorylation was not affected. Overall, our findings suggest that EK5 inhibits MMP-9 production through the nuclear-targeted down-regulation of NF-κB signaling in human monocytic cells and this may provide a novel molecular basis of EK5 activity. Further studies are needed to verify its anti-inflammatory effects.
原文英語
頁(從 - 到)403-412
頁數10
期刊Chemico-Biological Interactions
184
發行號3
DOIs
出版狀態已發佈 - 三月 2010

ASJC Scopus subject areas

  • Toxicology

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