DOI QR코드

DOI QR Code

Effect of Ullmus macrocarpa Hance Ethanol extract (Ulmus) on Improvement of allergic responses in RBL-2H3 mast Cells

RBL-2H3 비만세포에서 유백피 에탄올 추출물의 알레르기 반응 개선에 대한 효과

  • Do, Hyun Ju (New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation) ;
  • Oh, Tae Woo (Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM))
  • 도현주 (대구경북첨단의료산업진흥재단 신약개발지원센터) ;
  • 오태우 (한국한의학연구원 한의기술응용센터)
  • Received : 2021.10.15
  • Accepted : 2021.11.19
  • Published : 2021.11.30

Abstract

Objectives : In this study, we investigate the anti-allergic effects of Ullmus macrocarpa Hance (Ulmus) on RBL-2H3 mast cell (basophilic leukemia cell line), which are mediated by FcεRIs. Methods : We evaluated the effect of the ethanol extract of Ulmus on the allergic inflammatory response in IgE-antigen-mediated RBL-2H3 cells. Cell toxicity was determined by MTT assay and the markers of degranulation such as beta-hexosaminidase, histamine, PGD2, TNF-α, IL-4, IL-6 production of inflammatory mediators and FcεRI-mediated protein expression by western blot. Results : Ulmus inhibited degranulation and production of allergic mediators (e.g., TNF-α, IL-4, and IL-6) in them. Ulmus reduced histamine levels, expression of FcεRI signaling-related genes such as Lyn, Syk, and Fyn, and extracellular signal-regulated kinase phosphorylation in mast cells. Also, Ulmus reduced PGD2 release and cyclooxygenase-2 expression, and cytosolic phospholipase A2 phosphorylation in FcεRI-mediated RBL-2H3 mast cells. Conclusions : These results indicate that Ulmus exhibits anti-allergic activity through inhibition of degranulation and inflammatory mediators and cytokine release. These findings suggest that Ulmus may have potential as a prophylactic and therapeutic agent for the treatment of various allergic diseases.

Keywords

Acknowledgement

본 연구는 2021년도 정부(과학기술정보통신부)의 재원으로 한국연구재단의 지원을 받아 수행된 연구로(No. 2021R1C1C1012018), 이에 감사드립니다.

References

  1. Dykewicz MS, Fineman S, NicklasR, Lee R, Blessing-Moore J, Li JT. Executive summary of joint task force practice parameters on diagnosis and management of rhinitis. Ann Allergy Asthma Immunol. 1998;81:463-468. https://doi.org/10.1016/S1081-1206(10)63152-3
  2. Korean Journal of Asthma, Allergy and Clinical Immunology. Asthma and Allergy disease. Seoul: koonja publisher. 2002;66:431-433.
  3. Galli SJ. New concepts about the mast cell. N Engl J Med. 1993; 328(4): 257-265. https://doi.org/10.1056/NEJM199301283280408
  4. KM Ahn. Role of mast cell in allergic inflammation and innate immunity. Korean Journal of Pediatrics. 2004;47:11-15.
  5. Poole JA, Rosenwasser LJ. The role of immunoglobulin E and immune inflammation : implications in allergic rhinitis. Curr Allergy Asthma Rep. 2005;5(3):252-258. https://doi.org/10.1007/s11882-005-0045-5
  6. Lin K, Huang D, Huang D, Tzeng S and Lin W. Inhibition of ampk through lyn-syk-akt enhances fcεri signal pathways for allergic response. J Mol Med. 2016;94:183-194. https://doi.org/10.1007/s00109-015-1339-2
  7. Ahn DK, Nac HS. Oriental medicine and immunology. Paju:openbooks. 1994:15-48.
  8. Jun CD, Pae HO, Kim YC, Jeong SJ, Yoo JC, Lee EJ, Choi BM, Chae SW, Park RK, Chung HT. Inhibition of nitric oxide synthesis by butanolfraction ofthe methanol extract of Ulmus davidiana in murine macrophages. J Ethnopharmacol. 1998;62:129-135. https://doi.org/10.1016/S0378-8741(98)00063-4
  9. Choi SY, Lee S, Choi WH, Lee Y, Jo YO, Ha TY. Isolationand anti-inflammatory activity of Bakuchiolfrom Ulmus davidiana var. japonica. J Med Food. 2010;13:1019-1023. https://doi.org/10.1089/jmf.2009.1207
  10. Lee SJ, Lim KT. Glycoprotein isolated from Ulmus davidiana Nakai regulates expression of iNOS and COX-2 in vivo and in vitro. Food Chem Toxicol. 2007;45:990-1000. https://doi.org/10.1016/j.fct.2006.12.006
  11. Kim KS, Lee SD, Kim KH, Kil SY, Chung KH, Kim CH. Suppressive effects of a water extract of Ulmus davidiana Planch (Ulmaceae) on collageninduced arthritis in mice. J Ethnopharmacol. 2005;97:65-71. https://doi.org/10.1016/j.jep.2004.10.011
  12. Zheng MS, Li G, Li Y, Seo CS, Lee YK, Jung JS, Song DK, Bae HB, Kwak SH, Chang HW, Kim JR, Son JK. Protective constituents against sepsis in mice from the root barks of Ulmus davidiana var. japonica. Arch Pharm Res. 2011; 34:1443-1450. https://doi.org/10.1007/s12272-011-0905-6
  13. Kim JP, Kim WG, Koshino H, Jung J, Yoo ID. Sesquiterpene O-naphthoquinones from the root bark of Ulmus davidiana. Phytochemistry. 1996;43: 425-430. https://doi.org/10.1016/0031-9422(96)00279-8
  14. Busse WWW, Lemanske RF Jr. Asthma. N Engl J. Med. 2001;44(5):350-62.
  15. Moon SH, Jang HJ, Park YS, Lee WY, Lim DH, Kim JH. Fractional exhaled nitric oxide in Korean children with allergic rhinitis. Allergy Asthma Respir Dis. 2015;3(6):439-445. https://doi.org/10.4168/aard.2015.3.6.439
  16. Woo HS, Kim CH. The Review of Oriental Medical Therapy on Allergic Rhinitis. J Korean Oriental Med.2006;27(1):155-64.
  17. Kay AB. Allergy and allergic diseases. First of two parts. N Engl J Med 2001; 344(1): 30-37. https://doi.org/10.1056/NEJM200101043440106
  18. Gurish MF, Austen KF. The diverse roles of mast cells. J Exp Med 2001; 194(1): F1-5. https://doi.org/10.1084/jem.194.1.1
  19. Lee E, Chol EJ, Cheong H, Kim YR, Ryu SY, Kim KM. Anti-allergic actions of the leaves of castanea crenata and isolation of an active component responsible for the inhibition of mast cell degranulation. Archives of Pharmacal Research. 1999;22:320-323. https://doi.org/10.1007/BF02976372
  20. Beaven MA, Rogers J, Moore JP, Hesketh TR, Smith GA, Metcalfe JC. The mechanism of the calcium signal and correlation with histamine release in 2H3 cells. J. Biol. Chem. 1984;259: 7129-7136. https://doi.org/10.1016/S0021-9258(17)39847-2
  21. Salamon P, Shoham NG, Gavrieli R, Wolach B, Mekori YA. Human mast cells release interleukin-8 and induce neutrophilchemotaxis on contact with activated T cells. Allergy. 2005;60:1316-1319. https://doi.org/10.1111/j.1398-9995.2005.00886.x
  22. Mekori YA, Metcalfe DD. Mast cells in innate immunity. Immunol Rev. 2000;173: 131-140. https://doi.org/10.1034/j.1600-065X.2000.917305.x
  23. Toru H, Pawankar R, Ra C, Yata J, Nakahata T. Human mast cells produce IL-13 by high-affinity IgE receptor cross-linking:enhanced IL-13 production by IL-4-primed human mast cells. J Allergy Clin Immunol. 1998;102:491-502. https://doi.org/10.1016/S0091-6749(98)70140-X
  24. Fukui, H. Progress in Allergy Signal Research on Mast Cells: Up-Regulation of Histamine Signal-Related Gene Expression in Allergy Model Rats. J Pharmacol Sci. 2008;106(3):325-331. https://doi.org/10.1254/jphs.FM0070184
  25. Boyce, J.A. Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation. Immunol Rev. 2007;217(1):168-185. https://doi.org/10.1111/j.1600-065X.2007.00512.x
  26. Murphy, R.C., Gijon, M.A. Biosynthesis and metabolism of leukotrienes. Biochem J. 2007; 405(3):379-395. https://doi.org/10.1042/BJ20070289
  27. Ra C, Jouvin MH, Kinet JP. Complete structure of the mouse mast cell receptor for IgE (Fc epsilon RI) and surface expression of chimeric receptors (rat-mouse-human) on transfected cells. J Biol Chem. 1989;264(26):15323-15327. https://doi.org/10.1016/S0021-9258(19)84829-9
  28. Paolini R, Jouvin MH, Kinet JP. Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engantigenement and disengantigenement. Nature. 1991;353:855-858. https://doi.org/10.1038/353855a0
  29. Gilfillan AM, Tkaczyk C. Integrated signalling pathways for mast-cell activation. Nat. Rev. Immunol. 2006;6:218-230. https://doi.org/10.1038/nri1782
  30. Theoharidies TC, Kalogeromitros D. The critical role of mast cells in allergy and inflammation. Ann. N.Y. Acad. Sci. 2006;1088:78-99. https://doi.org/10.1196/annals.1366.025