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Costunolide inhibits cyclooxygenase-2 expression induced by toll-like receptor 3 or 4 agonist

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Abstract

Toll-like receptors (TLRs) play an important role in the induction of innate immune responses recognizing conserved microbial structural molecules. The microbial pathogens trigger the activation of two downstream signaling pathways of TLRs; myeloid differential factor 88 (MyD88)- and toll interleukin-1 receptor domain containing adapter inducing interferon-β (TRIF)-dependent pathways leading to the activation of nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3). Saussureae Radix has been used for centuries to treat a variety of diseases. Costunolide, one of the active ingredients in Saussureae Radix, has been used to treat many chronic diseases. However, the mechanism of costunolide’s beneficial effects is largely unknown. Here, we report biochemical evidence that costunolide inhibits NF-κB activation and cyclooxygenase-2 expression induced by the TLR3 agonist polyriboinosinic polyribocytidylic acid (poly[I : C]) or the TLR4 agonist lipopolysaccharide (LPS). These results suggest that costunolide can modulate the immune responses regulated by TLR signaling pathways.

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References

  1. Medzhitov, R. Toll-like receptors and innate immunity.Nat Rev Immunol 1, 135–145 (2001).

    Article  PubMed  CAS  Google Scholar 

  2. O’Neill, L. A. TLRs: Professor Mechnikov, sit on your hat.Trends Immunol 25, 687–693 (2004).

    Article  PubMed  Google Scholar 

  3. Vogel, S. N., Fitzgerald, K. A. & Fenton, M. J. TLRs: Differential adapter utilization by toll-like receptors mediates TLR-specific patterns of gene expression.Mol Interv 3, 466–477 (2003).

    Article  PubMed  CAS  Google Scholar 

  4. Takeda, K. & Akira, S. Toll-like receptors in innate immunity.Int Immunol 17, 1–14 (2005).

    Article  PubMed  CAS  Google Scholar 

  5. Lin, R., Heylbroeck, C., Pitha, P. M. & Hiscott, J. Virus-dependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome-mediated degradation.Mol Cell Biol bd18, 2986–2996 (1998).

    Google Scholar 

  6. Navarro, L. & David, M. p38-dependent activation of interferon regulatory factor 3 by lipopolysaccharide.J Biol Chem 274, 35535–35538 (1999).

    Article  PubMed  CAS  Google Scholar 

  7. Kawai, T.et al. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes.J Immunol 167, 5887–5894 (2001).

    PubMed  CAS  Google Scholar 

  8. Gao, J. J.et al. Autocrine/paracrine IFN-alphabeta mediates the lipopolysaccharide-induced activation of transcription factor Stat1alpha in mouse macrophages: Pivotal role of Stat1alpha in induction of the inducible nitric oxide synthase gene.J Immunol 161, 4803–4810 (1998).

    PubMed  CAS  Google Scholar 

  9. Pandey, M. M., Rastogi, S. & Rawat, A. K. Saussurea costus: Botanical, chemical and pharmacological review of an ayurvedic medicinal plant.J Ethnopharmacol 110, 379–390 (2007).

    Article  PubMed  CAS  Google Scholar 

  10. Matsuda, H.et al. Effects of sesquiterpenes and amino acid-sesquiterpene conjugates from the roots of Saussurea lappa on inducible nitric oxide synthase and heat shock protein in lipopolysaccharide-activated macrophages.Bioorg Med Chem 11, 709–715 (2003).

    Article  PubMed  CAS  Google Scholar 

  11. Kang, J. S., Yoon, Y. D., Lee, K. H., Park, S. K. & Kim, H. M. Costunolide inhibits interleukin-1beta expression by down-regulation of AP-1 and MAPK activity in LPS-stimulated RAW 264.7 cells.Biochem Biophys Res Commun 313, 171–177 (2004).

    Article  PubMed  CAS  Google Scholar 

  12. Lee, M. G., Lee, K. T., Chi, S. G. & Park, J. H. Costunolide induces apoptosis by ROS-mediated mitochondrial permeability transition and cytochrome C release.Biol Pharm Bull 24, 303–306 (2001).

    Article  PubMed  CAS  Google Scholar 

  13. Chen, H. C., Chou, C. K., Lee, S. D., Wang, J. C. & Yeh, S. F. Active compounds from Saussurea lappa Clarks that suppress hepatitis B virus surface antigen gene expression in human hepatoma cells.Antiviral Res 27, 99–109 (1995).

    Article  PubMed  CAS  Google Scholar 

  14. Ahn, S. I., Lee, J. K. & Youn, H. S. Inhibition of homodimerization of toll-like receptor 4 by 6-shogaol.Mol Cells 27, 211–215 (2009).

    Article  PubMed  CAS  Google Scholar 

  15. Ahn, S. I. & Youn, H. S. Guggulsterone suppresses the activation of NF-κB and expression of COX-2 induced by toll-like receptor 2, 3, and 4 agonists.Food Sci Biotechnol 17, 1294–1298 (2008).

    CAS  Google Scholar 

  16. Youn, H. S.et al. Specific inhibition of MyD88-independent signaling pathways of TLR3 and TLR4 by resveratrol: Molecular targets are TBK1 and RIP1 in TRIF complex.J Immunol 175, 3339–3346 (2005).

    PubMed  CAS  Google Scholar 

  17. Youn, H. S., Saitoh, S. I., Miyake, K. & Hwang, D. H. Inhibition of homodimerization of Toll-like receptor 4 by curcumin.Biochem Pharmacol 72, 62–69 (2006).

    Article  PubMed  CAS  Google Scholar 

  18. Simmons, D. L., Levy, D. B., Yannoni, Y. & Erikson, R. L. Identification of a phorbol ester-repressible vsrc-inducible gene.Proc Natl Acad Sci USA 86, 1178–1182 (1989).

    Article  PubMed  CAS  Google Scholar 

  19. Vane, J. R., Bakhle, Y. S. & Botting, R. M. Cyclooxygenases 1 and 2.Annu Rev Pharmacol Toxicol 38, 97–120 (1998).

    Article  PubMed  CAS  Google Scholar 

  20. Murakami, A. & Ohigashi, H. Targeting NOX, INOS and COX-2 in inflammatory cells: Chemoprevention using food phytochemicals.Int J Cancer 121, 2357–2363 (2007).

    Article  PubMed  CAS  Google Scholar 

  21. Kawai, T. & Akira, S. Toll-like receptor and RIG-I-like receptor signaling.Ann N Y Acad Sci 1143, 1–20 (2008).

    Article  PubMed  CAS  Google Scholar 

  22. Kawai, T. & Akira, S. Signaling to NF-kappaB by Toll-like receptors.Trends Mol Med 13, 460–469 (2007).

    Article  PubMed  CAS  Google Scholar 

  23. Fitzgerald, K. A.et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway.Nat Immunol 4, 491–496 (2003).

    Article  PubMed  CAS  Google Scholar 

  24. Meylan, E.et al. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappaB activation.Nat Immunol 5, 503–507 (2004).

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Hyung-Sun Youn.

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Park, SJ., Yun, SM., Lee, AN. et al. Costunolide inhibits cyclooxygenase-2 expression induced by toll-like receptor 3 or 4 agonist. Toxicol. Environ. Health. Sci. 1, 122–126 (2009). https://doi.org/10.1007/BF03216473

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