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http://dx.doi.org/10.5483/BMBRep.2011.44.7.468

Suppression of the TRIF-dependent signaling pathway of toll-like receptors by (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate  

Park, Se-Jeong (Department of Medical Science, Soonchunhyang University)
Park, Hye-Jeong (Department of Biomedical Laboratory Science, Soonchunhyang University)
Kim, Soo-Jung (Department of Biomedical Laboratory Science, Soonchunhyang University)
Shin, Hwa-Jeong (Department of Medical Science, Soonchunhyang University)
Min, In-Soon (Department of Healthcare Management, College of Medical Sciences, Soonchunhyang University)
Koh, Kwang-Oh (Department of Chemistry, College of Natural Sciences, Soonchunhyang University)
Kim, Dae-Young (Department of Chemistry, College of Natural Sciences, Soonchunhyang University)
Youn, Hyung-Sun (Department of Medical Science, Soonchunhyang University)
Publication Information
BMB Reports / v.44, no.7, 2011 , pp. 468-472 More about this Journal
Abstract
Toll-like receptors (TLRs) are pattern recognition receptors that recognize molecular structures derived from microbes and initiate innate immunity. TLRs have two downstream signaling pathways, the MyD88- and TRIF-dependent pathways. Dysregulated activation of TLRs is closely linked to increased risk of many chronic diseases. Previously, we synthesized fumaryl pyrrolidinone, (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate (IPOP), which contains a fumaric acid isopropyl ester and pyrrolidinone, and demonstrated that it inhibits the activation of nuclear factor kappa B by inhibiting the MyD88-dependent pathway of TLRs. However, the effect of IPOP on the TRIF-dependent pathway remains unknown. Here, we report the effect of IPOP on signal transduction via the TRIF-dependent pathway of TLRs. IPOP inhibited lipopolysaccharide- or polyinosinic-polycytidylic acidinduced interferon regulatory factor 3 activation, as well as interferon-inducible genes such as interferon inducible protein-10. These results suggest that IPOP can modulate the TRIF-dependent signaling pathway of TLRs, leading to decreased inflammatory gene expression.
Keywords
Fumaryl pyrrolidinone; Lipopolysaccharide; Polyinosinicpolycytidylic acid; Toll-like receptor; TRIF;
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1 Youn, H. S., Saitoh, S. I., Miyake, K. and Hwang, D. H. (2006) Inhibition of homodimerization of Toll-like receptor 4 by curcumin. Biochem. Pharmacol. 72, 62-69.   DOI   ScienceOn
2 Yun, S. M., Kang, S. H., Lee, A. N., Park, S. J., Kim, D. Y. and Youn, H. S. (2010) Suppression of Toll-like receptor 2 or 4 agonist-induced cyclooxygenase-2 expression by 4-oxo-4-(2-oxo-oxazolidin-3-yl)-but-2-enoic acid ethyl ester. Int. Immunopharmacol. 10,163-168.   DOI   ScienceOn
3 Katsuyama, K., Kojima, R., Yokoyama, S., Yanai, M., Sueda, N., Sugita, M., Momose, K. and Yamada, H. (1998) N2733, 1-[3-(3-pyridyl)-acryloyl]-2-pyrrolidinone hydrochloride inhibits LPS-induced TNF-alpha production and improves survival in endotoxemic mice. Biosci. Biotechnol. Biochem. 62, 2177-2181.   DOI   ScienceOn
4 Katsuyama, K. and Hirata, Y. (2001) A pyrrolidinone derivative inhibits cytokine-induced iNOS expression and NF-kappaB activation by preventing phosphorylation and degradation of IkappaB-alpha. J. Biochem. 129, 585-591.   DOI   ScienceOn
5 Stetson, D. B. and Medzhitov, R. (2006) Type I interferons in host defense. Immunity 25, 373-381.   DOI   ScienceOn
6 Wietek, C. and O'Neill, L. A. (2007) Diversity and regulation in the NF-kappaB system. Trends. Biochem. Sci. 32, 311-319.   DOI   ScienceOn
7 Honda, K. and Taniguchi, T. (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern- recognition receptors. Nat. Rev. Immunol. 6, 644-658.   DOI   ScienceOn
8 Evans, D. A., Scheidt, K. A., Johnston, J. N. and Willis, M. C. (2001) Enantioselective and diastereoselective Mukaiyama- Michael reactions catalyzed by bis(oxazoline) copper( II) complexes. J. Am. Chem. Soc. 123, 4480-4491.   DOI   ScienceOn
9 Kang, S. H., Kang, Y. K. and Kim, D. Y. (2009) Catalytic enantioselective conjugate addition of aromatic amines to fumarate derivatives: asymmetric synthesis of aspartic acid derivatives. Tetrahedron 65, 5676-5679.   DOI   ScienceOn
10 Youn, H. S., Ahn, S. I. and Lee, B. Y. (2009) Guggulsterone suppresses the activation of transcription factor IRF3 induced by TLR3 or TLR4 agonists. Int. Immunopharmacol. 9, 108-112.   DOI   ScienceOn
11 Akira, S., Uematsu, S. and Takeuchi, O. (2006) Pathogen recognition and innate immunity. Cell 124, 783-801.   DOI   ScienceOn
12 Ahn, S. I., Lee, J. K. and Youn, H. S. (2009) Inhibition of homodimerization of toll-like receptor 4 by 6-shogaol. Mol. Cells 27, 211-215.   과학기술학회마을   DOI
13 Bjorkbacka, H., Fitzgerald, K. A., Huet, F., Li, X., Gregory, J. A., Lee, M. A., Ordija, C. M., Dowley, N. E., Golenbock, D. T. and Freeman, M. W. (2004) The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades. Physiol. Genomics 19, 319-330.   DOI   ScienceOn
14 Takeda, K. and Akira, S. (2005) Toll-like receptors in innate immunity. Int. Immunol. 17, 1-14.
15 Kawai, T., Takeuchi, O., Fujita, T., Inoue, J., Muhlradt, P. F., Sato, S., Hoshino, K. and Akira, S. (2001) 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.   DOI
16 Gao, J. J., Filla, M. B., Fultz, M. J., Vogel, S. N., Russell, S. W. and Murphy, W. J. (1998) 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.
17 Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S. M. and Maniatis, T. (2003) IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 4, 491-496.
18 Lee, A. N., Park, S. J., Koh, K. O., Kim, D. Y. and Youn, H. S. (2011) Suppression of cyclooxygenase-2 expression induced by Toll-like receptor 2 or 4 agonists by (E)-isopropyl 4-oxo-4-(2-oxopyrrolidin-1-yl)-2-butenoate. Mol. Cell Toxicol. 7, 39-44.   DOI
19 Medzhitov, R., Preston-Hurlburt, P. and Janeway, C. A., Jr. (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-397.   DOI   ScienceOn
20 Chi, Z. L., Hayasaka, S., Zhang, X. Y., Hayasaka, Y. and Cui, H. S. (2004) Effects of rolipram, a selective inhibitor of type 4 phosphodiesterase, on lipopolysaccharide- induced uveitis in rats. Invest. Ophthalmol. Vis. Sci. 45, 2497-2502.   DOI   ScienceOn