Suppressive effect of tamarixetin, isolated from Inula japonica, on degranulation and eicosanoid production in bone marrow-derived mast cells

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Shunli Pan
Eujin Lee
Youn Ju Lee
Meihua Jin
Eunkyung Lee


Degranulation, Leukotriene C4 (LTC4), Prostaglandin D2 (PGD2), mast cells


Background: The aim of this study was to evaluate the inhibitory effect of tamarixetin on the production of inflammatory mediators in IgE/antigen-induced mouse bone marrow-derived mast cells (BMMCs).
Materials and methods: The effects of tamarixetin on mast cell activation were investigated with regard to degranulation, eicosanoid generation, Ca2+ influx, and immunoblotting of vari-ous signaling molecules.
Results: Tamarixetin effectively decreased degranulation and the eicosanoid generation such as leukotriene C4 and prostaglandin D2 in BMMCs. To elucidate the mechanism involved, we investigated the effect of tamarixetin on the phosphorylation of signal molecules. Tamarixetin inhibited the phosphorylation of Akt and its downstream signal molecules including IKK and nuclear factor κB. In addition, tamarixetin downregulated the phosphorylation of cytosolic phospholipase A2 (cPLA2) and p38 mitogen-activated protein kinase.
Conclusions: Taken together, this study suggests that tamarixetin inhibits degranulation and eicosanoid generation through the PLCγ1 as well as Akt pathways in BMMCs, which would be potential for the prevention of allergic inflammatory diseases.

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1. Boyce JA. Mast cells: beyond IgE. J Allergy Clin Immunol. 2003;111:24–32; quiz 33.
2. Kalesnikoff J, Galli SJ. New developments in mast cell biology. Nat Immunol. 2008;9:1215–1223.
3. Gilfillan AM, Rivera J. The tyrosine kinase network regulating mast cell activation. Immunol Rev. 2009;228:149–169.
4. Gilfillan AM, Tkaczyk C. Integrated signalling pathways for mast-cell activation. Nat Rev Immunol. 2006;6:218–230.
5. Soberman RJ, Christmas P. The organization and consequences of eicosanoid signaling. J Clin Invest. 2003;111:1107–1113.
6. Kim SG, Lee E, Park NY, Park HH, Jeong KT, Kim KJ, et al. Britanin attenuates ovalbumin-induced airway inflammation in a murine asthma model. Arch Pharmacal Res. 2016;39:1006– 1012.
7. Park HH, Kim MJ, Li Y, Park YN, Lee J, Lee YJ, et al. Britanin suppresses LPS-induced nitric oxide, PGE2 and cytokine pro-duction via NF-kappaB and MAPK inactivation in RAW 264.7 cells. Int Immunopharmacol. 2013;15:296–302. https://doi. org/10.1016/j.intimp.2012.12.005
8. Park HH, Kim SG, Park YN, Lee J, Lee YJ, Park NY, et al. Suppressive effects of britanin, a sesquiterpene compound isolated from Inulae flos, on mast cell-mediated inflamma-tory responses. Am J Chin Med. 2014;42:935–947. https://doi. org/10.1142/S0192415X14500591
9. Park HH, Kim SG, Kim MJ, Lee J, Choi BK, Jin MH, et al. Suppressive effect of tomentosin on the production of inflammatory mediators in RAW264.7 cells. Biol Pharm Bull. 2014;37:1177–1183.
10. Min BS, Cuong TD, Lee JS, Shin BS, Woo MH, Hung TM. Cholinesterase inhibitors from Cleistocalyx operculatus buds. Arch Pharm Res. 2010;33:1665–1670. s12272-010-1016-5
11. Nessa F, Ismail Z, Mohamed N. Xanthine oxidase inhibitory activities of extracts and flavonoids of the leaves of Blumea balsamifera. Pharm Biol. 2010;48:1405–1412. 0.3109/13880209.2010.487281
12. Park HJ, Lee SJ, Cho J, Gharbi A, Han HD, Kang TH, et al. Tamarixetin Exhibits antiinflammatory activity and pre-vents bacterial sepsis by increasing IL-10 production. J Nat Prod. 2018;81:1435–1443. jnatprod.8b00155
13. Jeong KT, Kim SG, Lee J, Park YN, Park HH, Park NY, et al. Anti-allergic effect of a Korean traditional medicine, Biyeom-Tang on mast cells and allergic rhinitis. BMC Complement Altern Med. 2014;14:54.
14. Jeong KT, Lee E, Park NY, Kim SG, Park HH, Lee J, et al. Imperatorin suppresses degranulation and eicosanoid generation in activated bone marrow-derived mast cells. Biomol Ther (Seoul). 2015;23:421–427. biomolther.2015.023
15. Metcalfe DD, Peavy RD, Gilfillan AM. Mechanisms of mast cell signaling in anaphylaxis. J Allergy Clin Immunol. 2009;124:639–646; quiz 647–648. jaci.2009.08.035
16. Fischer L, Poeckel D, Buerkert E, Steinhilber D, Werz O. 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. 2005;1736:109–119.
17. Flamand N, Lefebvre J, Surette ME, Picard S, Borgeat P. Arachidonic acid regulates the translocation of 5-lipoxygenase to the nuclear membranes in human neutrophils. J Biol Chem. 2006;281:129–136.
18. Suram S, Gangelhoff TA, Taylor PR, Rosas M, Brown GD, Bonventre JV, et al. Pathways regulating cytosolic phospholi-pase A2 activation and eicosanoid production in macrophages by Candida albicans. J Biol Chem. 2010;285:30676–30685.
19. Ashraf M, Murakami M, Kudo I. Cross-linking of the high-affinity IgE receptor induces the expression of cyclo-oxygenase 2 and attendant prostaglandin generation requiring interleukin 10 and interleukin 1 beta in mouse cultured mast cells. Biochem J. 1996;320:965–973.
20. Moon TC, Murakami M, Ashraf MD, Kudo I, Chang HW. 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. 1998;185:146–152. https://
21. Reddy ST, Wadleigh DJ, Herschman HR. Transcriptional regulation of the cyclooxygenase-2 gene in activated mast cells. J Biol Chem. 2000;275:3107–3113. jbc.275.5.3107
22. Lu Y, Li Y, Seo CS, Murakami M, Son JK, Chang HW. Saucerneol D inhibits eicosanoid generation and degranula-tion through suppression of Syk kinase in mast cells. Food Chem Toxicol. 2012;50:4382–4388. fct.2012.08.053
23. Lu Y, Yang JH, Li X, Hwangbo K, Hwang SL, Taketomi Y, et al. Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation. Biochem Pharmacol. 2011;82:1700–1708.