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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: mol.105.021048v1 69/6/1783    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kim, J.-H. Articles by Lee, W.-h. Search for Related Content PubMed PubMed Citation Articles by Kim, J.-H. Articles by Lee, W.-h.

Decursin Inhibits Induction of Inflammatory Mediators by Blocking Nuclear Factor-B Activation in Macrophages

Department of Genetic Engineering, College of Natural Sciences (J.-H.K, J.-H.J., S.-T.J., H.K., W.L.), Department of Pharmacology, College of Medicine (J.O., K.S.), and Department of Agricultural Chemistry, College of Agricultural Biotechnology (S.-I.K., K.-S.S.), Kyungpook National University, Taegu, Korea

In the course of screening inhibitors of matrix metalloproteinase (MMP)-9 induction in macrophages, we isolated decursin, a coumarin compound, from the roots of Angelicae gigas. As a marker for the screening and isolation, we tested expression of MMP-9 in RAW264.7 cells and THP-1 cells after treatment with bacterial lipopolysaccharide (LPS), the TLR-4 ligand. Decursin suppressed MMP-9 expression in cells stimulated by LPS in a dose-dependent manner at concentrations below 60 µM with no sign of cytotoxicity. The suppressive effect of decursin was observed not only in cells stimulated with ligands for TLR4, TLR2, TLR3, and TLR9 but also in cells stimulated with interleukin (IL)-1, and tumor necrosis factor (TNF)-, indicating that the molecular target of decursin is common signaling molecules induced by these stimulants. In addition to the suppression of MMP-9 expression, decursin blocked nitric oxide production and cytokine (IL-8, MCP-1, IL-1, and TNF-) secretion induced by LPS. To find out the molecular mechanism responsible for the suppressive effect of decursin, we analyzed signaling molecules involved in the TLR-mediated activation of MMP-9 and cytokines. Decursin blocked phosphorylation of IB and nuclear translocation of NF-B in THP-1 cells activated with LPS. Furthermore, expression of a luciferase reporter gene under the promoter containing NF-B binding sites was blocked by decursin. These data indicate that decursin is a novel inhibitor of NF-B activation in signaling induced by TLR ligands and cytokines.

Received for publication November 22, 2005.

Accepted for publication March 1, 2006.

Address correspondence to: Dr. Won-Ha Lee, Department of Genetic Engineering, Kyungpook National University, Taegu 702-701, Korea. E-mail: whl{at}knu.ac.kr