期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 184, 期 3, 页码 403-412出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2010.01.010
关键词
NF-kappa B; MMP-9; TNF-alpha; Monocyte
资金
- National Science Council of Taiwan [NSC96-2320-B-038-021-MY3]
- Taiwan Department of Health Clinical Trial and Research Center of Excellence [DOH99-TD-B-111-004]
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-kappa B (NF-kappa B). 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)-alpha stimulated expression of MMP-9 in a human monocytic cell line, THP-1. Our results show that TNF-alpha-induced expression of MMP-9 at both mRNA and protein levels was completely blocked by EK5 in a concentration-dependent (1-20 mu M) manner. We also found that EK5 markedly suppressed NF-kappa B signaling as detected by the NF-kappa B reporter gene assay but had no effects on the degradation of IKB alpha or translocation of NF-kappa B. 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-kappa B 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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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