Biomedical Science Letters (대한의생명과학회지)

The Korean Society for Biomedical Laboratory Sciences (대한의생명과학회)
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Parthenolide Suppresses the Expression of Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Induced by Toll-Like Receptor 2 and 4 Agonists

  • Lee, A-Neum (Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University) ;
  • Park, Se-Jeong (Department of Medical Science, College of Medical Sciences, Soonchunhyang University) ;
  • Yun, Sae-Mi (Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University) ;
  • Lee, Mi-Young (Department of Medical Biotechnology, College of Medical Sciences, Soonchunhyang University) ;
  • Son, Bu-Soon (Department of Environmental Health Science, College of Natural Sciences, Soonchunhyang University) ;
  • Youn, Hyung-Sun (Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University)
  • ;
  • ;
  • ;
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  • 윤형선 (순천향대학교 의료과학대학 임상병리학과)
  • Received : 2009.12.14
  • Accepted : 2010.03.23
  • Published : 2010.03.31
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Abstract

Toll-like receptors (TLRs), which are pattern recognition receptors (PRRs), recognize pathogen-associated molecular patterns (PAMPs) and regulate the activation of innate immunity. All TLR signaling pathways culminate in the activation of NF-${\kappa}B$, leading to the induction of inflammatory gene products such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Parthenolide, a sesquiterpene lactone isolated from the herb feverfew (Tanacetum parthenium), has been used as folk remedies to treat many chronic diseases for many years. In the present report, we present biochemical evidence that parthenolide inhibits the NF-${\kappa}B$ activation induced by TLR agonists and the overexpression of downstream signaling components of TLRs, MyD88, $IKK{\beta}$, and p65. Parthenolide also inhibits TLR agonists-induced COX-2 and iNOS expression. These results suggest that parthenolide can modulate the immune responses regulated by TLR signaling pathways.

Keywords

References

  1. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006. 124: 783-801. https://doi.org/10.1016/j.cell.2006.02.015
  2. Beutler BA. TLRs and innate immunity. Blood. 2009. 113: 1399 -1407.
  3. Bork PM, Schmitz ML, Kuhnt M, Escher C, Heinrich M. Sesquiterpene lactone containing Mexican Indian medicinal plants and pure sesquiterpene lactones as potent inhibitors of transcription factor NF-kappaB. FEBS Lett. 1997. 402: 85-90. https://doi.org/10.1016/S0014-5793(96)01502-5
  4. Fitzgerald KA, McWhirter SM, Faia KL, Rowe DC, Latz E, Golenbock DT, Coyle AJ, Liao SM, Maniatis T. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat lmmunol. 2003. 4: 491-496. https://doi.org/10.1038/ni921
  5. Groenewegen WA, Heptinstall S. A comparison of the effects of an extract of feverfew and parthenolide, a component of feverfew, on human platelet activity in-vitro. J Pharm Pharmacol. 1990. 42: 553-557. https://doi.org/10.1111/j.2042-7158.1990.tb07057.x
  6. Harris RE, Beebe-Donk J, Doss H, Burr Doss D. Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review). Oncol Rep. 2005. 13: 559-583.
  7. Hehner SP, Heinrich M, Bork PM, Vogt M, Ratter F, Lehmann V, Schulze-Osthoff K, Droge W, Schmitz ML. Sesquiterpene lactones specifically inhibit activation of NF-kappa B by preventing the degradation of I kappa B-alpha and I kappa B-beta. J BioI Chern. 1998. 273: 1288-1297. https://doi.org/10.1074/jbc.273.3.1288
  8. Heinrich M, Robles M, West JE, Ortiz de Montellano BR, Rodriguez E. Ethnopharmacology of Mexican asteraceae (Compositae). Annu Rev Pharmacol Toxicol. 1998. 38: 539 -565. https://doi.org/10.1146/annurev.pharmtox.38.1.539
  9. Kawai T, Akira S. Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med. 2007. 13: 460-469. https://doi.org/10.1016/j.molmed.2007.09.002
  10. Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. The dorsoventral regulatory gene cassette spatzie/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell. 1996. 86: 973-983. https://doi.org/10.1016/S0092-8674(00)80172-5
  11. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature. 2007. 449: 819-826. https://doi.org/10.1038/nature06246
  12. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, Tschopp J. RIPl is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat lmmunol. 2004. 5: 503-507. https://doi.org/10.1038/ni1061
  13. Murphy JJ, Heptinstall S, Mitchell JR. Randomised double-blind placebo-controlled trial of feverfew in migraine prevention. Lancet. 1988. 2: 189-192.
  14. Naesdal J, Brown K. NSAlD-associated adverse effects and acid control aids to prevent them: a review of current treatment options. Drug Saf. 2006. 29: 119-132. https://doi.org/10.2165/00002018-200629020-00002
  15. Oka D, Nishimura K, Shiba M, Nakai Y, Arai Y, Nakayama M, Takayama H, Inoue H, Okuyama A, Nonomura N. Sesquiterpene lactone parthenolide suppresses tumor growth in a xenograft model of renal cell carcinoma by inhibiting the activation of NF-kappaB. Int J Cancer. 2007. 120: 2576 -2581. https://doi.org/10.1002/ijc.22570
  16. Pahl HL. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene. 1999. 18: 6853-6866. https://doi.org/10.1038/sj.onc.1203239
  17. Sato S, Sugiyama M, Yamamoto M, Watanabe Y, Kawai T, Takeda K, Akira S. Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRlF) associates with TNF receptorassociated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and lFNregulatory factor-3, in the Toll-like receptor signaling. J lmmunol. 2003. 171: 4304-4310.
  18. Schinella GR, Giner RM, Recio MC, Mordujovich de Buschiazzo P, Rios JL, Manez S. Anti-inflammatory effects of South American Tanacetum vulgare. J Pharm Pharmacol. 1998. 50: 1069-1074. https://doi.org/10.1111/j.2042-7158.1998.tb06924.x
  19. Sheehan M, Wong HR, Hake PW, Malhotra V, O'Connor M, Zingarelli B. Parthenolide, an inhibitor of the nuclear factorkappaB pathway, ameliorates cardiovascular derangement and outcome in endotoxic shock in rodents. Mol Pharmacol. 2002. 61: 953-963. https://doi.org/10.1124/mol.61.5.953
  20. Takeda K, Akira S. Toll-like receptors in innate immunity. Int Tmmunol. 2005. 17: 1-14.
  21. Youn HS, Lee JY, Saitoh SI, Miyake K, Hwang DH. Auranofin, as an anti-rheumatic gold compound, suppresses LPS-induced homodimerization of TLR4. Biochem Biophys Res Commun. 2006a. 350: 866-871. https://doi.org/10.1016/j.bbrc.2006.09.097
  22. Youn HS, Lee JY, Saitoh SI, Miyake K, Kang KW, Choi YJ, Hwang DH. Suppression of MyD88- and TRIF-dependent signaling pathways of Toll-like receptor by ( -)epigallocatechin- 3-gallate, a polyphenol component of green tea. Biochem Pharmacol. 2006b. 72: 850-859. https://doi.org/10.1016/j.bcp.2006.06.021
  23. Youn HS, Saitoh SI, Miyake K, Hwang DH. Inhibition of homodimerization of Toll-like receptor 4 by curcumin. Biochem Pharmacol. 2006c. 72: 62-69. https://doi.org/10.1016/j.bcp.2006.03.022