The Inhibitory effects of quail egg on mast cells degranulation by suppressing PAR2-mediated MAPK and NF-kB activation
Background: Quail egg (QE) has been reported to possess an anti-allergic and anti-inflammatory activity. We have demonstrated that whole QE was able to attenuate the allergic symptoms in food allergy–induced EoE murine model, but whether QE albumen or QE yolk plays a more important role still remains unclear.
Objective: In this current study, we investigated the suppressive role of QE in mast cell degranulation and cytokine production of the effect phase response.
Method: A passive cutaneous anaphylaxis (PCA) mouse model was used to confirm the anti-allergic effect of QE. Besides, HMC-1 cell model was used to study its suppressive role in more detail. In this in vitro study, we divided QE into three groups: whole QE, QE albumen, and QE yolk. The effect of QE treatment on mast cell degranulation and intracellular calcium influx was investigated. Moreover, the effect of QE allergy– related mediators, genes, and proteins were also assessed by ELISA, RT-PCR, and western blotting.
Results and discussion: Our data showed that the extent of mast cell degranulation–mediated ear vascular permeability in IgE-mediated PCA mice treated with whole QE (17 mg/kg) was decreased significantly up to 43.31 ± 0.42% reduction. HMC-1 cell–based immunological assay in vitro indicated that QE, particularly its albumen, acted as a ‘mast cell stabilizer’. Under the concentration of 70 μg/mL, QE albumen effectively suppressed the releases of β-hexosaminidase, histamine, and tryptase, as well as Th2 and pro-inflammatory cytokine production; reached 30 up to 50% reduction. Besides, QE albumen was also able to significantly modulate the upregulation of IL-10 up to 58.30 ± 5.9%. Interestingly, our data indicated that QE yolk still had a significant inhibitory effect on modulating Th2 cytokines in its highest concentration (100 μg/mL), while QE albumen showed no inhibitory effect. Western blot analysis showed QE albumen effectively down-regulated the expressions of calcium- related protein (TRPC1, Orai1, STIM1, PLC-γ and IP3R), facilitated the reduction of PAR-2 and induced the reduction of phosphorylation of JNK, IKKα, p50 and p65 protein expressions.
Conclusion: As confirmed by PCA and HMC-1 cell-based immunology assay, QE albumen and QE yolk may work together through exerting anti-allergy activity and can be used as a potential anti-allergic nutrient in the future.
- Theoharides TC, Kalogeromitros D. The critical role of mast cells in allergy and inflammation. Ann N Y Acad Sci 2006; 1088: 78–99.
- Minai-Fleminger MY, Schaffer FL. Mast cells and eosinophils: the two key effector cells in allergic inflammation. Inflamm Res 2009; 58(10). 631–8.
- Cook EB, Stahl JL, Barney NP, Graziano FM. Mechanisms of antihistamines and mast cell stabilizers in ocular allergic inflammation. Curr Drug Targets Inflamm Allergy 2002; 1(2): 167–80.
- Feeney RE, Means GE, Bigler JC. Inhibition of human trypsin, plasmin, and thrombin by naturally occurring inhibitors of proteolytic enzymes. J Biol Chem 1969; 244(8): 1957–60.
- Bruttman G. ‘Ovix’ Quail egg homogenate: a clinical evaluation. La Medicina Biologica 1995; 2: 25–9.
- Vergnaud S, Bruttmann G. Effetto inibitorio dell’ovomucoide di uovo di quaglia gaipponese sull’attivita. La Medicina Biologica 2007; 2: 5–13.
- Melsens P, Waterloo BE, Jean L, Saint-Junien FR. Anti-inflammatory composition for modulating the cell response of neutrophils and eosinophils. United States Patent, US2015/0057232. 2015.
- Truffier JC. Approche therapeutique de la maladie allergique par ingestion d'oeufs de caille. La Clinique 1978; 22: 2–4.
- Benichou AC, Armanet M, Bussiere A, Chevreau N, Cardot JM, Tetard J. A proprietary blend of quail egg for the attenuation ofnasal provocation with a standardized allergenic challenge: a randomized, double-blind, placebo-controlled study. Food Sci Nutr 2014; 2(6): 655–63.
- Knoops L, Louahed J, van Snick J, Renauld JC. IL-9 promotes but is not necessary for sytemic anaphylaxis. J Immunol 2005; 175(1): 335–41.
- Integrative Therapeutics. ALLQLEARTM Fast-acting seasonal support Therapeutics Integrative http://data.integrativepro.com/product-literature/info/allqlear-info-sheet.pdf (cited: 12.06.2016).
- FDA. Guidance for industry-estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Department of Health and Human Services, Food and Drug Administration; 2005. Available from: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM078932.pdf.
- Tominaga H, Ishiyama M, Ohseto F, Sasamoto K, Hamamoto T, Suzuki K, et al. A water-soluble tetrazolium salt useful for colorimetric cell viability assay. Anal Comm 1999; 36(2): 47–50.
- Hohman RJ, Dreskin SC. Measuring degranulation of mast cells. Curr Protocols Immunol 2001; 26(7): 1–7.
- Kuehn HS, Radinger M, Gilfillan AM. Measuring mast cell mediator release. Curr Protocols Immunol 2010;7:38.
- Huber M, Helgason MP, Scheid V, Duronio R, Humphries RK, Krystal G. Targeted disruption of SHIP leads to steel factor-induced degranulation of mast cells. Eur Mol Biol Organ J 1998; 17(24): 7311–9.
- Mahmood T, Yang PC. Western Blot: technique, theory, and trouble shooting. N Am J Med Sci 2012; 4(9): 429–34.
- Schroeder JT. Basophils: emerging roles in the pathogenesis of allergic disease. Immunol Rev 2011; 242(1): 144–60.
- Masuda A, Yoshikai Y, Aiba K, Matsuguchi T. Th2 cytokine production from mast cells is directly induced by lipopolysaccharide and distincly regulated by c-Jun N-Terminal Kinase and p38 pathways. J Immunol 2002; 169(7): 3801–10.
- Grimbaldeston ME, Nake S, Kalesnikoff J, Tsai M, Galli SJ. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat Immunol 2007; 8(10): 1095–104.
- Theoharides TC. Mast cells and inflammation. Biochimica et Biophysica Acta 2012; 1822(1): 21–33.
- Vig M, Kinet JP. Calcium signaling in immune cells. Nat Immunol 2009; 10(1): 21–7.
- Jacquet A. The role of innate immunity activation in house dust mite allergy. Trends Mol Med 2011; 17(10): 604–11.
- Liu WH, Means GE, Feeney ER. The inhibitory properties of avian ovoinhibitors against proteolytic enzymes. Biochimica et Biophysica Acta 1971; 229(1): 176–85.
- Bogard WC, Kato I, Laskowski M. A Ser162/Gly162 polymorphism in Japanese quail ovomucoid. J Biol Chem 1980; 255(14): 6569–74.
- Tolik D, Polawska E, Charuta A, Nowaczewski S, Cooper R. Characteristics of egg parts, chemical composition and nutritive value of Japanese quail eggs-a review. Folia Biologica (Krakow) 2014; 62(4): 287–92.
- Park GH, Jeon SJ, Ryu JR, Choi MS, Han SH, Yang SI, et al. Essential role of mitogen-activated protein kinase pathways in protease activated receptor 2-mediated nitric-oxide production from rat primary astrocytes. Nitric Oxide 2009; 21(2): 110–9.
- Hu S, Qiu N, Liu Y, Zhao H, Gao D, Song R, et al. Identification and comparative proteomic study of quail and duck egg white protein using 2-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry analysis. Poultry Sci 2016; 95(5): 1137–44.
- Sun C, Liu J, Li W, Xu G, Yang N. Divergent proteome patterns of egg albumen from domestic chicken, duck, goose, turkey, quail, and pigeon. Proteomics 2017; 17(17–18); 1–12.
- Liou J, Kim M, Heo W, Jones J, Myers JW, Ferrell JE, et al. STIM is a Ca2+ sensor essential for Ca2+ store depletion triggered Ca2+ influx. Curr Biol 2005; 15(13): 1235–41.
- Yuan JP, Zeng W, Dorwart MR, Choi Y J, Worley P F, Muallem S. SOAR and the polybasic STIM1 domains gate and regulate Orai channels. Nat Cell Biol 2009; 11(3); 337–43.
- Liao Y, Erxleben C, Yildirim E, Abramowitz J, Armstrong DL, Birnbaumer L. Orai proteins interact with TRPC channels and confer responsiveness to store depletion. Proc Natl Acad Sci U S A 2007; 104(11): 4682–7.
- Prakriya M. The molecular physiology of CRAC channels. Immunol Rev 2009; 231(1): 88–98.
- Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan Huberson M, et al. CRACM1 is a plasma membrane protein essential for store operated Ca2+ entry. Science 2006; 312(5777): 1220–3.
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