期刊
EXPERIMENTAL AND MOLECULAR MEDICINE
卷 41, 期 11, 页码 824-831出版社
NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2009.41.11.088
关键词
anti-inflammatory agents; ELAV-Iike protein 1; lipopolysaccharides; macrophages; quercetin; tumor necrosis factor-alpha
资金
- Ministry of Education, Science and Technology, Korea [M20706000020-07M0600-02010]
- BK21 program
- Seoul National University Hospital
Hu protein R (HuR) binds to the AU-rich element (ARE) in the 3'UTR to stabilize TNF-alpha mRNA. Here, we identified chemical inhibitors of the interaction between HuR and the ARE of TNF-alpha mRNA using RNA electrophoretic mobility gel shift assay (EMSA) and filter binding assay. Of 179 chemicals screened, we identified three with a half-maximal inhibitory concentration (IC50) below 10 mu M. The IC50 of quercetin, b-40, and b-41 were 1.4, 0.38, and 6.21 mu M, respectively, for binding of HuR protein to TNF-alpha mRNA. Quercetin and b-40 did not inhibit binding of tristetraprolin to the ARE of TNF-alpha mRNA. When LPS-treated RAW264.7 cells were treated with quercetin and b-40, we observed decreased stability of TNF-alpha mRNA and decreased levels of secreted TNF-alpha. From these results, we could find inhibitors for the TNF-alpha mRNA stability, which might be used advantageously for both the study for post-transcriptional regulation and the discovery of new anti-inflammation drugs.
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