Browse > Article
http://dx.doi.org/10.1007/s10059-009-0130-z

Suppression of the TRIF-Dependent Signaling Pathway of Toll-Like Receptors by Isoliquiritigenin in RAW264.7 Macrophages  

Park, Se-Jeong (Departments of Medical Science, College of Medical Sciences, Soonchunhyang University)
Song, Ho-Yeon (Department of Microbiology, School of Medicine, Soonchunhyang University)
Youn, Hyung-Sun (Departments of Medical Science, College of Medical Sciences, Soonchunhyang University)
Publication Information
Molecules and Cells / v.28, no.4, 2009 , pp. 365-368 More about this Journal
Abstract
Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-${\beta}$ (TRIF)-dependent downstream signaling pathways. Isoliquiritigenin (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-${\kappa}B$ and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.
Keywords
isoliquiritigenin; lipopolysaccharide; polyinosinic-polycytidylic acid; Toll-like receptors; TRIF;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 4  (Related Records In Web of Science)
연도 인용수 순위
1 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. (2004b). The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades. Physiol. Genomics 19, 319-330   DOI   ScienceOn
2 Kumar, S., Sharma, A., Madan, B., Singhal, V., and Ghosh, B. (2007). Isoliquiritigenin inhibits IkappaB kinase activity and ROS generation to block TNF-alpha induced expression of cell adhesion molecules on human endothelial cells. Biochem. Pharmacol. 73, 1602-1612   DOI   ScienceOn
3 Lin, R., Heylbroeck, C., Pitha, P.M., and Hiscott, J. (1998). Virusdependent phosphorylation of the IRF-3 transcription factor regulates nuclear translocation, transactivation potential, and proteasome- mediated degradation. Mol. Cell. Biol. 18, 2986-2996   DOI
4 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   PUBMED   ScienceOn
5 Navarro, L., and David, M. (1999). p38-dependent activation of interferon regulatory factor 3 by lipopolysaccharide. J. Biol. Chem. 274, 35535-35538   DOI   ScienceOn
6 Schafer, S.L., Lin, R., Moore, P.A., Hiscott, J., and Pitha, P.M. (1998). Regulation of type I interferon gene expression by interferon regulatory factor-3. J. Biol. Chem. 273, 2714-2720   DOI   ScienceOn
7 Vaya, J., Belinky, P.A., and Aviram, M. (1997). Antioxidant constituents from licorice roots: isolation, structure elucidation and antioxidative capacity toward LDL oxidation. Free Radic. Biol. Med. 23, 302-313   DOI   ScienceOn
8 Lin, R., Heylbroeck, C., Genin, P., Pitha, P.M., and Hiscott, J. (1999). Essential role of interferon regulatory factor 3 in direct activation of RANTES chemokine transcription. Mol. Cell. Biol. 19, 959-966   DOI
9 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   DOI   ScienceOn
10 Takahashi, T., Takasuka, N., Iigo, M., Baba, M., Nishino, H., Tsuda, H., and Okuyama, T. (2004). Isoliquiritigenin, a flavonoid from licorice, reduces prostaglandin E2 and nitric oxide, causes apoptosis, and suppresses aberrant crypt foci development. Cancer Sci. 95, 448-453   DOI   ScienceOn
11 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. (2004a). The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades. Physiol. Genomics 19, 319-330   DOI   ScienceOn
12 Takeda, K., and Akira, S. (2005). Toll-like receptors in innate immunity. Int. Immunol. 17, 1-14
13 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
14 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 IFNregulatory factor 3 and the expression of a subset of lipopolysaccharide- inducible genes. J. Immunol. 167, 5887-5894   DOI
15 Kim, J.Y., Park, S.J., Yun, K.J., Cho, Y.W., Park, H.J., and Lee, K.T. (2008). Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of NF-kappaB in RAW 264.7 macrophages. Eur. J. Pharmacol. 584, 175-184   DOI   ScienceOn
16 Akira, S., Uematsu, S., and Takeuchi, O. (2006). Pathogen recognition and innate immunity. Cell 124, 783-801   DOI   ScienceOn
17 Uematsu, S., and Akira, S. (2007). Toll-like receptor and innate immunity. Seikagaku 79, 769-776   PUBMED
18 Kakegawa, H., Matsumoto, H., and Satoh, T. (1992). Inhibitory effects of some natural products on the activation of hyaluronidase and their anti-allergic actions. Chem. Pharm. Bull. 40, 1439-1442   DOI   PUBMED   ScienceOn
19 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
20 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
21 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   DOI   ScienceOn