Browse > Article
http://dx.doi.org/10.4062/biomolther.2014.038

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway  

Lu, Yue (School of Pharmacy, Shanghai University of Traditional Chinese Medicine)
Li, Xian (College of Pharmacy, Yeungnam University)
Park, Young Na (College of Pharmacy, Yeungnam University)
Kwon, Okyun (College of Pharmacy, Yeungnam University)
Piao, Donggen (College of Pharmacy, Yeungnam University)
Chang, Young-Chae (Department of Pathology, Catholic University of Daegu School of Medicine)
Kim, Cheorl-Ho (Department of Biological Science, Sungkyunkwan University)
Lee, Eunkyung (Research and Development Division, Korean Promotion Institute for Traditional Medicine Industry)
Son, Jong Keun (College of Pharmacy, Yeungnam University)
Chang, Hyeun Wook (College of Pharmacy, Yeungnam University)
Publication Information
Biomolecules & Therapeutics / v.22, no.3, 2014 , pp. 193-199 More about this Journal
Abstract
The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin $D_2$ ($PGD_2$), leukotriene $C_4$ ($LTC_4$), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of $PGD_2$ and $LTC_4$ in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun $NH_2$-terminal kinase and p38), and the nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.
Keywords
Britanin; Mast cells; Eicosanoid; Degranulation; Syk kinase; Mitogen-activated protein kinase; Allergic inflammation;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Moon, T. C., Murakami, M., Ashraf, M. D., Kudo, I. and Chang, H. W. (1998) Regulation of cyclooxygenase-2 and endogenous cytokine expression by bacterial lipopolysaccharide that acts in synergy with c-kit ligand and Fc epsilon receptor I crosslinking in cultured mast cells. Cell. Immunol. 185, 146-152.   DOI   ScienceOn
2 Park, H. H., Kim, M. J., Li, Y., Park, Y. N., Lee, J., Lee, Y. J., Kim, S. G., Park, H. J., Son, J. K., Chang, H. W. and Lee, E. (2013) Britanin suppresses LPS-induced nitric oxide, PGE2 and cytokine production via NF-${\kappa}B$ and MAPK inactivation in RAW 264.7 cells. Int. Immunopharmacol. 15, 296-302.   DOI
3 Park, Y. N., Lee, Y. J., Choi, J. H., Jin, M., Yang, J. H., Li, Y., Lee, J., Li, X., Kim, K. J., Son, J. K., Chang, H. W., Kim, J. Y. and Lee, E. (2011) Alleviation of OVA-induced airway inflammation by flowers of Inula japonica in a murine model of asthma. Biosci. Biotechnol. Biochem. 75, 871-876.   DOI   ScienceOn
4 Reddy, S. T., Wadleigh, D. J. and Herschman, H. R. (2000) Transcriptional regulation of the cyclooxygenase-2 gene in activated mast cells. J. Biol. Chem. 275, 3107-3113.   DOI   ScienceOn
5 Ruzza, P., Biondi, B. and Calderan, A. (2009) Therapeutic prospect of Syk inhibitors. Expert Opin. Ther. Pat. 19, 1361-1376.   DOI
6 Shan, J. J., Yang, M. Ren, J. W. (2006) Anti-diabetic and hypolipidemic effects of aqueous-extract from the flower of Inula japonica in alloxan-induced diabetic mice. Biol. Pharm. Bull. 29, 455-459.   DOI   ScienceOn
7 Siraganian, R. P. (2003) Mast cell signal transduction from the highaffinity IgE receptor. Curr. Opin. Immunol. 15, 639-646.   DOI   ScienceOn
8 Song, Q. H., Kobayashi, T., Iijima, K., Hong, T. and Cyong, J. C. (2000) Hepatoprotective effects of Inula britannica on hepatic injury in mice. Phytother. Res. 14, 180-186.   DOI   ScienceOn
9 Tak, P. P. and Firestein, G. S. (2001) NF-kappaB: a key role in inflammatory diseases. J. Clin. Invest. 107, 7-11.   DOI   ScienceOn
10 Jin, H. Z., Lee, D., Lee, J. H., Lee, K., Hong, Y. S., Choung, D. H., Kim, Y. H. and Lee, J. J. (2006) New sesquiterpene dimers from Inula britannica inhibit NF-kappaB activation and NO and TNFalpha production in LPS-stimulated RAW264.7 cells. Planta Med. 72, 40-45.   DOI   ScienceOn
11 Kobayashi, T., Song, Q. H., Hong, T., Kitamura, H. and Cyong, J. C. (2002) Preventative effects of the flowers of Inula britannica on autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of streptozotocin. Phytother. Res. 16, 377-382.   DOI   ScienceOn
12 Lin, L. L., Wartmann, M., Lin, A. Y., Knopf, J. L., Seth, A. and Davis, R. J. (1993) cPLA2 is phosphorylated and activated by MAP kinase. Cell 72, 269-278.   DOI   ScienceOn
13 Liu, S., Liu, H., Yan, W., Zhang, L., Bai, N. and Ho, C. T. (2004) Studies on 1-O-acetylbritannilactone and its derivative, (2-O-butyloxime-3- phenyl)-propionyl-1-O-acetylbritannilactone ester. Bioorg. Med. Chem. Lett. 14, 1101-1104.   DOI   ScienceOn
14 Liu, Y. P., Wen, J. K., Zheng, B., Zhang, D. Q. and Han, M. (2007) Acetylbritannilactone suppresses lipopolysaccharide-induced vascular smooth muscle cell inflammatory response. Eur. J. Pharmacol. 577, 28-34.   DOI
15 Lu, Y., Li, Y., Jin, M., Yang, J. H., Li, X., Chao, G. H., Park, H. H., Park, Y. N., Son, J. K., Lee, E. and Chang, H. W. (2012a) Inula japonica extract inhibits mast cell-mediated allergic reaction and mast cell activation. J. Ethnopharmacol. 143, 151-157.   DOI   ScienceOn
16 Lu, Y., Li, Y., Seo, C. S., Murakami, M., Son, J. K. and Chang, H. W. (2012b) Saucerneol D inhibits eicosanoid generation and degranulation through suppression of Syk kinase in mast cells. Food Chem. Toxicol. 50, 4382-4388.   DOI
17 Choi, J. H., Park, Y. N., Li, Y., Jin, M. H., Lee, J, Lee, Y, Son, J, K., Chang, H. W. and Lee, E. (2010) Flowers of Inula japonica attenuate inflammatory responses. Immune Netw. 10, 145-152.   DOI
18 Lu, Y., Yang, J. H., Li, X., Hwangbo, K., Hwang, S. L., Taketomi, Y., Murakami, M., Chang, Y. C., Kim, C. H., Son, J. K, and Chang, H. W. (2011) Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation. Biochem. Pharmacol. 82, 1700-1708.   DOI
19 Mandal, A. K., Skoch, J., Bacskai, B. J., Hyman, B. T., Christmas, P., Miller, D., Yamin, T. T., Xu, S., Wisniewski, D., Evans, H. F. and Soberman, R. J. (2004) The membrane organization of leukotriene synthesis. Proc. Natl. Acad. Sci. U.S.A. 101, 6587-6592.   DOI
20 Masuda, E. S. and Schmitz, J. (2008) Syk inhibitors as treatment for allergic rhinitis. Pulm. Pharmacol. Ther. 21, 461-467.   DOI   ScienceOn
21 Clark, J. D., Lin, L. L., Kriz, R. W., Ramesha, C. S., Sultzman, L. A., Lin, A. Y., Milona, N. and Knopf, J. L. (1991) A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP. Cell 65, 1043-1051.   DOI
22 Cruse, G., Kaur, D., Yang, W., Duffy, S. M., Brightling, C. E. and Brad ding, P. (2005) Activation of human lung mast cells by monomeric immunoglobulin E. Eur. Respir. J. 25, 858-863.   DOI   ScienceOn
23 Dennis, E. A. (1997) The growing phospholipase A2 superfamily of signal transduction enzymes. Trends Biochem. Sci. 22, 1-2.   DOI
24 Bajpai, M., Chopra, P., Dastidar, S. G. and Ray, A. (2008) Spleen tyrosine kinase: a novel target for therapeutic intervention of rheumatoid arthritis. Expert Opin. Investig. Drugs 17, 641-659.   DOI
25 Flamand, N., Lefebvre, J., Surette, M. E., Picard, S. and Borgeat, P. (2006) Arachidonic acid regulates the translocation of 5-lipoxygenase to the nuclear membranes in human neutrophils. J. Biol. Chem. 281, 129-136.   DOI
26 Han, J. W., Lee, B. G., Kim, K. Y., Yoon, J. W., Jin, H. K., Hong, S., Lee, H. Y., Lee, K. R. and Lee, H. W. (2001) Ergolide, sesquiterpene lactone from Inula britannica, inhibits inducible nitric oxide synthase and cyclo-oxygenase-2 expression in RAW 264.7 macrophages through the inactivation of NF-kappaB. Br. J. Pharmacol. 133, 503-512.   DOI   ScienceOn
27 Hwang, S. L., Li, X., Lu, Y., Jin, Y., Jeong, Y. T., Kim, Y. D., Lee, I. K., Taketomi, Y., Sato, H., Cho, Y. S., Murakami, M. and Chang, H. W. (2013) AMP-activated protein kinase negatively regulates Fc$\varepsilon$RImediated mast cell signaling and anaphylaxis in mice. J. Allergy Clin. Immunol. 132, 729-736.   DOI
28 Fischer, L., Poeckel, D., Buerkert, E., Steinhilber, D. and Werz, O. (2005) Inhibitors of actin polymerisation stimulate arachidonic acid release and 5-lipoxygenase activation by upregulation of Ca2+ mobilisation in polymorphonuclear leukocytes involving Src family kinases. Biochim. Biophys. Acta 1736, 109-119.   DOI   ScienceOn
29 Wong, B. R., Grossbard, E. B., Payan, D. G. and Masuda, E. S. (2004) Targeting Syk as a treatment for allergic and autoimmune disorders. Expert Opin. Investig. Drugs 13, 743-762.   DOI   ScienceOn