Browse > Article
http://dx.doi.org/10.14348/molcells.2015.0062

The Genome-Wide Expression Profile of Saussurea lappa Extract on House Dust Mite-Induced Atopic Dermatitis in Nc/Nga Mice  

Lim, Hye-Sun (K-herb Research Center, Korea Institute of Oriental Medicine)
Ha, Hyekyung (K-herb Research Center, Korea Institute of Oriental Medicine)
Shin, Hyeun-Kyoo (K-herb Research Center, Korea Institute of Oriental Medicine)
Jeong, Soo-Jin (Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine)
Publication Information
Molecules and Cells / v.38, no.9, 2015 , pp. 765-772 More about this Journal
Abstract
Saussurea lappa has been reported to possess anti-atopic properties. In this study, we have confirmed the S. lappa's anti-atopic properties in Nc/Nga mice and investigated the candidate gene related with its properties using microarray. We determined the target gene using real time PCR in in vitro experiment. S. lappa showed the significant reduction in atoptic dermatitis (AD) score and immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of microarray using back skin obtained from animals, we found that S. lappa's properties are closely associated with cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT-PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa-treated mice. Among these genes, PI3Kca and $IL20R{\beta}$ were significantly downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment using HaCaT cells, we found that the S. lappa components, including alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone significantly decreased the expression of PI3Kca but not $IL20R{\beta}$ in vitro. Therefore, our study suggests that PI3Kca-related signaling is closely related with the protective effects of S. lappa against the development of atopic-dermatitis.
Keywords
atopic dermatitis; microarray; Nc/Nga mouse model; PI3Kca; Saussurea lappa;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Bader, A.G., Kang, S., Zhao, L., and Vogt, P.K. (2005). Oncogenic PI3K deregulates transcription and translation. Nat. Rev. Cancer 5, 921-929.   DOI   ScienceOn
2 Barnes, K.C. (2010). An update on the genetics of atopic dermatitis: scratching the surface in 2009. J. Allergy Clin. Immunol. 125, 16-29.e11-11; quiz 30-11.   DOI   ScienceOn
3 Borden, E.C., Sen, G.C., Uze, G., Silverman, R.H., Ransohoff, R.M., Foster, G.R., and Stark, G.R. (2007). Interferons at age 50: past, current and future impact on biomedicine. Nat. Rev. Drug Discov. 6, 975-990.   DOI   ScienceOn
4 Burchill, M.A., Yang, J., Vang, K.B., and Farrar, M.A. (2007). Interleukin-2 receptor signaling in regulatory T cell development and homeostasis. Immunol. Lett. 114, 1-8.   DOI   ScienceOn
5 Byambaragchaa, M., Dela Cruz, J., Kh, A., and Hwang, S.G. (2014). Anticancer potential of an ethanol extract of saussurea involucrata against hepatic cancer cells in vitro. Asian Pac. J. Cancer Prev. 15, 7527-7532.   DOI   ScienceOn
6 Chen, H.C., Chou, C.K., Lee, S.D., Wang, J.C., and Yeh, S.F. (1995). Active compounds from Saussurea lappa Clarks that suppress hepatitis B virus surface antigen gene expression in human hepatoma cells. Antiviral Res. 27, 99-109.   DOI   ScienceOn
7 Choi, J.S., Roh, J.Y., and Lee, J.R. (2014). Clinical availability of component-resolved diagnosis using microarray technology in atopic dermatitis. Ann. Dermatol. 26, 437-446.   DOI   ScienceOn
8 Choy, D.F., Hsu, D.K., Seshasayee, D., Fung, M.A., Modrusan, Z., Martin. Z., Liu, F.T., and Arron, J.R. (2012). Comparative transcriptomic analyses of atopic dermatitis and psoriasis reveal shared neutrophilic inflammation. J. Allergy Clin. Immunol. 130, 1335-1343.   DOI   ScienceOn
9 Cookson, W.O. (2001). The genetics of atopic dermatitis: strategies, candidate genes, and genome screens. J. Am. Acad. Dermatol. 45, S7-9.   DOI   ScienceOn
10 Dumoutier, L., Leemans, C., Lejeune, D., Kotenko, S.V., and Renauld, J.C. (2001). Cutting edge: STAT activation by IL-19, IL-20 and mda-7 through IL-20 receptor complexes of two types. J. Immunol. 167, 3545-3549.   DOI
11 Engelman, J.A., Luo, J., and Cantley, L.C. (2006). The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet. 7, 606-619.
12 Isaksen, D.E., Baumann, H., Zhou, B., Nivollet, S., Farr, A.G., Levin, S.D., and Ziegler, S.F. (2002). Uncoupling of proliferation and Stat5 activation in thymic stromal lymphopoietin-mediated signal transduction. J. Immunol. 168, 3288-3294.   DOI
13 Fung-Leung, W.P. (2011). Phosphoinositide 3-kinase delta (PI3Kdelta) in leukocyte signaling and function. Cell. Signal. 23, 603-608.   DOI   ScienceOn
14 Heinzmann, A., Mao, X.Q., Akaiwa, M., Kreomer, R.T., Gao, P.S., Ohshima, K., Umeshita, R., Abe, Y., Braun, S., Yamashita, T., et al. (2000). Genetic variants of IL-13 signalling and human asthma and atopy. Hum. Mol. Genet. 9, 549-559.   DOI   ScienceOn
15 Holmes, K., Roberts, O.L., Thomas, A.M., and Cross, M.J. (2007). Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. Cell. Signal. 19, 2003-2012.   DOI   ScienceOn
16 Kim, C.S., Sohn, S.H., Jeon, S.K., Kim, K.N., Ryu, J.J., and Kim, M.K. (2006) .Effect of various implant coatings on biological responses in MG63 using cDNA microarray. J. Oral Rehabil. 33, 368-379.   DOI   ScienceOn
17 Kim, H.R., Kim, J.M., Kim, M.S., Hwang, J.K., Park, Y.J., Yang, S.H., Kim, H.J., Ryu, D.G., Lee, D.S., Oh, H., et al. (2014). Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-kappaB-dependent MMP-9 expression in MCF-7 breast cancer cells. BMC Complement. Altern. Med. 14, 170.   DOI   ScienceOn
18 Lasagni, L., Francalanci, M., Annunziato, F., Lazzeri, E., Giannini, S., Cosmi, L., Sagrinati, C., Mazzinghi, B., Orlando, C., Maggi, E., et al. (2003). An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J. Exp. Med. 197, 1537-1549.   DOI   ScienceOn
19 Leung, D.Y., Bieber, T. (2003). Atopic dermatitis. Lancet 361, 151-160.   DOI   ScienceOn
20 Lee, J.K., Ha, H., Lee, H.Y., Park, S.J., Jeong, S.L., Choi, Y.J., Shin, H.K. (2010). Inhibitory effects of heartwood extracts of Broussonetia kazinoki Sieb on the development of atopic dermatitis in NC/Nga mice. Biosci. Biotechnol. Biochem. 74, 1802-1806.   DOI   ScienceOn
21 Lim, H.S., Ha, H., Lee, M.Y., Jin, S.E., Jeong, S.J., Jeon, W.Y., Shin, N.R., Sok, D.E., Shin, H.K. (2014). Saussurea lappa alleviates inflammatory chemokine production in HaCaT cells and house dust mite-induced atopic-like dermatitis in Nc/Nga mice. Food Chem. Toxicol. 63, 212-220.   DOI   ScienceOn
22 Lindblad-Toh, K., Wade, C.M., Mikkelsen, T.S., Karlsson, E.K., Jaffe, D.B., Kamal, M., Clamp, M., Chang, J.L., Kulbokas, E.J. 3rd, Zody, M.C., et al. (2005). Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438, 803-819.   DOI   ScienceOn
23 Liu, L.Y., Mathur, S.K., Sedgwick, J.B., Jarjour, N.N., Busse, W.W., Kelly, E.A. (2006). Human airway and peripheral blood eosinophils enhance Th1 and Th2 cytokine secretion. Allergy 61, 589-597.   DOI   ScienceOn
24 Lu, B., Humbles, A., Bota, D., Gerard, C., Moser, B., Soler, D., Luster, A.D., and Gerard, N.P. (1999). Structure and function of the murine chemokine receptor CXCR3. Eur. J. Immunol. 29, 3804-3812.   DOI
25 Lu, Z.R., Kim, W.S., Cho, I.H., Park, D., Bhak, J., Shi, L., Zhou, H.W., Lee, D.Y., Park, Y.D., Yang, J.M., et al. (2009). DNA microarray analyses and interactomic predictions for atopic dermatitis. J. Dermatol. Sci. 55, 123-125.   DOI   ScienceOn
26 Matesanz, F., Fedetz, M., Collado-Romero, M., Fernandez, O., Guerrero, M., Delgado, C., and Alcina, A. (2001). Allelic expression and interleukin-2 polymorphisms in multiple sclerosis. J. Neuroimmunol. 119, 101-105.   DOI   ScienceOn
27 Sano, S., Chan, K.S., Carbajal, S., Clifford, J., Peavey, M., Kiguchi, K., Itami, S., Nickoloff, B.J., and DiGiovanni, J. (2005). Stat3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model. Nat. Med. 11, 43-49.   DOI   ScienceOn
28 Nashed, B.F., Zhang, T., Al-Alwan, M., Srinivasan, G., Halayko, A.J., Okkenhaug, K., Vanhaesebroeck, B., Hayglass, K.T., and Marshall, A.J. (2007). Role of the phosphoinositide 3-kinase p110delta in generation of type 2 cytokine responses and allergic airway inflammation. Eur. J. Immunol. 37, 416-424.   DOI   ScienceOn
29 Novak, N., Tepel, C., Koch, S., Brix, K., Bieber, T., and Kraft, S. (2003). Evidence for a differential expression of the FcepsilonRIgamma chain in dendritic cells of atopic and nonatopic donors. J. Clin. Invest. 111, 1047-1056.   DOI
30 Sa, S.M., Valdez, P.A., Wu, J., Jung, K., Zhong, F., Hall, L., Kasman, I., Winer, J., Modrusan, Z., Danilenko, D.M., et al. (2007). The effects of IL-20 subfamily cytokines on reconstituted human epidermis suggest potential roles in cutaneous innate defense and pathogenic adaptive immunity in psoriasis. J. Immunol. 178, 2229-2240.   DOI
31 Sebastian, K., Borowski, A., Kuepper, M., and Friedrich, K. (2008). Signal transduction around thymic stromal lymphopoietin (TSLP) in atopic asthma. Cell Commun. Signal. 6, 5.   DOI   ScienceOn
32 Tanimoto, T., Jin, Z.G., and Berk, B.C. (2002). Transactivation of vascular endothelial growth factor (VEGF) receptor Flk-1/KDR is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). J. Biol. Chem. 277, 42997-43001.   DOI   ScienceOn
33 Theofilopoulos, A.N., Baccala, R., Beutler, B., and Kono, D.H. (2005). Type I interferons (alpha/beta) in immunity and autoimmunity. Annu. Rev. Immunol. 23, 307-336.   DOI   ScienceOn
34 Zhang, Z.K., Yang, Y., Bai, S.R., Zhang, G.Z., Liu, T.H., Zhou, Z., Wang, C.M., Tang, L.J., Wang, J., and He, S.X. (2014). Screening for key genes associated with atopic dermatitis with DNA microarrays. Mol. Med. Rep. 9, 1049-1055.   DOI
35 Wang, Y., Barbacioru, C., Hyland, F., Xiao, W., Hunkapiller, K.L., Blake, J., Chan, F., Gonzalez, C., Zhang, L., and Samaha, R.R. (2006). Large scale real-time PCR validation on gene expression measurements from two commercial longoligonucleotide microarrays. BMC Genomics 7, 59.   DOI   ScienceOn
36 Yoshikawa, M., Hatakeyama, S., Inoue, Y., and Yamahara, J. (1993). Saussureamines A, B, C, D, and E, new anti-ulcer principles from Chinese Saussureae Radix. Chem. Pharm. Bull. 41, 214-216.   DOI   ScienceOn
37 Yu, W.S., Jeong, S.J., Kim, J.H., Lee, H.J., Song, H.S., Kim, M.S., Ko, E., Lee, H.J., Khil, J.H., et al. (2011). The genome-wide expression profile of 1,2,3,4,6-penta-O-galloyl-${\beta}$-D-glucosetreated MDA-MB-231 breast cancer cells: molecular target on cancer metabolism. Mol. Cells 32, 123-132.   DOI   ScienceOn
38 Zuo, L., Fulkerson, P.C., Finkelman, F.D., Mingler, M., Fischetti, C.A., Blanchard, C., and Rothenberg, M.E. (2010). IL-13 induces esophageal remodeling and gene expression by an eosinophilindependent, IL-13R alpha 2-inhibited pathway. J. Immunol. 185, 660-669.   DOI