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

Overview

Journal Biomol Ther (Seoul)

Specialty Pharmacology

Date 2014 Jul 11

PMID 25009699

Citations 9

Authors

Yue Lu

Xian Li

Young Na Park

Okyun Kwon

Donggen Piao

Young-Chae Chang

Cheorl-Ho Kim

Eunkyung Lee

Jong Keun Son

Hyeun Wook Chang

Affiliations

Soon will be listed here.

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 D2 (PGD2), leukotriene C4 (LTC4), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of PGD2 and LTC4 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 Cγ1 (PLCγ1)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun NH2-terminal kinase and p38), and the nuclear factor-κB (NF-κB) 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.

Citing Articles

Britanin - a beacon of hope against gastrointestinal tumors?.

Kajdanek A, Kolat D, Zhao L, Kciuk M, Pasieka Z, Kaluzinska-Kolat Z World J Clin Oncol. 2024; 15(4):523-530.

PMID: 38689621 PMC: 11056858. DOI: 10.5306/wjco.v15.i4.523.

Britanin inhibits titanium wear particle‑induced osteolysis and osteoclastogenesis.

Kim J, Lim S, Ihn H, Kim J, Yea K, Moon J Mol Med Rep. 2023; 28(5).

PMID: 37732549 PMC: 10539997. DOI: 10.3892/mmr.2023.13092.

The Complexity of Sesquiterpene Chemistry Dictates Its Pleiotropic Biologic Effects on Inflammation.

Arizmendi N, Alam S, Azyat K, Makeiff D, Befus A, Kulka M Molecules. 2022; 27(8).

PMID: 35458648 PMC: 9032002. DOI: 10.3390/molecules27082450.

Syk-Targeted, a New 3-Arylbenzofuran Derivative EAPP-2 Blocks Airway Inflammation of Asthma-COPD Overlap in vivo and in vitro.

Li S, Hui Y, Yuan J, Zhang Z, Li X, Fang N J Inflamm Res. 2021; 14:2173-2185.

PMID: 34079326 PMC: 8164447. DOI: 10.2147/JIR.S310875.

Brusatol Derivative-34 Attenuates Allergic Airway Inflammation Via Inhibition of the Spleen Tyrosine Kinase Pathway.

Ding Y, Tang W, Pei F, Fu L, Ma P, Bai J Front Pharmacol. 2021; 12:587417.

PMID: 33859559 PMC: 8042380. DOI: 10.3389/fphar.2021.587417.

References

Cruse G, Kaur D, Yang W, Duffy S, Brightling C, Bradding P . Activation of human lung mast cells by monomeric immunoglobulin E. Eur Respir J. 2005; 25(5):858-63. DOI: 10.1183/09031936.05.00091704. View

Moon T, Murakami M, Ashraf M, Kudo I, Chang H . 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(2):146-52. DOI: 10.1006/cimm.1998.1284. View

Reddy S, Wadleigh D, Herschman H . Transcriptional regulation of the cyclooxygenase-2 gene in activated mast cells. J Biol Chem. 2000; 275(5):3107-13. DOI: 10.1074/jbc.275.5.3107. View

Jin H, Lee D, Lee J, Lee K, Hong Y, Choung D . New sesquiterpene dimers from Inula britannica inhibit NF-kappaB activation and NO and TNF-alpha production in LPS-stimulated RAW264.7 cells. Planta Med. 2006; 72(1):40-5. DOI: 10.1055/s-2005-873189. View

Park Y, Lee Y, Choi J, Jin M, Yang J, Li Y . Alleviation of OVA-induced airway inflammation by flowers of Inula japonica in a murine model of asthma. Biosci Biotechnol Biochem. 2011; 75(5):871-6. DOI: 10.1271/bbb.100787. View

Shan J, Yang M, Ren J . Anti-diabetic and hypolipidemic effects of aqueous-extract from the flower of Inula japonica in alloxan-induced diabetic mice. Biol Pharm Bull. 2006; 29(3):455-9. DOI: 10.1248/bpb.29.455. View

Lu Y, Li Y, Jin M, Yang J, Li X, Chao G . Inula japonica extract inhibits mast cell-mediated allergic reaction and mast cell activation. J Ethnopharmacol. 2012; 143(1):151-7. DOI: 10.1016/j.jep.2012.06.015. View

Ruzza P, Biondi B, Calderan A . Therapeutic prospect of Syk inhibitors. Expert Opin Ther Pat. 2009; 19(10):1361-76. DOI: 10.1517/13543770903207039. View

Lu Y, Yang J, Li X, Hwangbo K, Hwang S, Taketomi Y . Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation. Biochem Pharmacol. 2011; 82(11):1700-8. DOI: 10.1016/j.bcp.2011.08.022. View

10.

Liu Y, Wen J, Zheng B, Zhang D, Han M . Acetylbritannilactone suppresses lipopolysaccharide-induced vascular smooth muscle cell inflammatory response. Eur J Pharmacol. 2007; 577(1-3):28-34. DOI: 10.1016/j.ejphar.2007.08.030. View

11.

Choi J, Park Y, Li Y, Jin M, Lee J, Lee Y . Flowers of Inula japonica Attenuate Inflammatory Responses. Immune Netw. 2010; 10(5):145-52. PMC: 2993946. DOI: 10.4110/in.2010.10.5.145. View

12.

Kobayashi T, Song Q, Hong T, Kitamura H, Cyong J . Preventative effects of the flowers of Inula britannica on autoimmune diabetes in C57BL/KsJ mice induced by multiple low doses of streptozotocin. Phytother Res. 2002; 16(4):377-82. DOI: 10.1002/ptr.868. View

13.

Mandal A, Skoch J, Bacskai B, Hyman B, Christmas P, Miller D . The membrane organization of leukotriene synthesis. Proc Natl Acad Sci U S A. 2004; 101(17):6587-92. PMC: 404089. DOI: 10.1073/pnas.0308523101. View

14.

Park H, Kim M, Li Y, Park Y, Lee J, Lee Y . Britanin suppresses LPS-induced nitric oxide, PGE2 and cytokine production via NF-κB and MAPK inactivation in RAW 264.7 cells. Int Immunopharmacol. 2012; 15(2):296-302. DOI: 10.1016/j.intimp.2012.12.005. View

15.

Hwang S, Li X, Lu Y, Jin Y, Jeong Y, Kim Y . AMP-activated protein kinase negatively regulates FcεRI-mediated mast cell signaling and anaphylaxis in mice. J Allergy Clin Immunol. 2013; 132(3):729-736.e12. DOI: 10.1016/j.jaci.2013.02.018. View

16.

Lin L, Wartmann M, Lin A, Knopf J, Seth A, Davis R . cPLA2 is phosphorylated and activated by MAP kinase. Cell. 1993; 72(2):269-78. DOI: 10.1016/0092-8674(93)90666-e. View

17.

Lu Y, Li Y, Seo C, Murakami M, Son J, Chang H . Saucerneol D inhibits eicosanoid generation and degranulation through suppression of Syk kinase in mast cells. Food Chem Toxicol. 2012; 50(12):4382-8. DOI: 10.1016/j.fct.2012.08.053. View

18.

Dennis E . The growing phospholipase A2 superfamily of signal transduction enzymes. Trends Biochem Sci. 1997; 22(1):1-2. DOI: 10.1016/s0968-0004(96)20031-3. View

19.

Liu S, Liu H, Yan W, Zhang L, Bai N, Ho C . Studies on 1-O-acetylbritannilactone and its derivative, (2-O-butyloxime-3-phenyl)-propionyl-1-O-acetylbritannilactone ester. Bioorg Med Chem Lett. 2004; 14(5):1101-4. DOI: 10.1016/j.bmcl.2003.12.078. View

20.

Siraganian R . Mast cell signal transduction from the high-affinity IgE receptor. Curr Opin Immunol. 2003; 15(6):639-46. DOI: 10.1016/j.coi.2003.09.010. View