, Volume 32, Issue 4, pp 211–217 | Cite as

Inhibitory Effect of Glycoprotein Isolated from Cudrania tricuspidata Bureau on Expression of Inflammation-Related Cytokine in Bisphenol A-Treated HMC-1 Cells



Cudrania tricuspidata is one of the most omnipresent traditional herbal drugs for anti-inflammation and anti-tumor. The purpose of the present study was to determine whether the CTB glycoprotein regulates the inflammatory reaction stimulated by bisphenol A (BPA) in human mast cells (HMC-1). Thus, we investigated that CTB glycoprotein inhibits the degranulation of histamine, expression of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), as a mitogen activated protein (MAP) kinase, nuclear transcription factors involving nuclear factor (NF)-κB and Activator protein (AP)-1, cyclooxygenase (COX)-2. The results indicated that CTB glycoprotein decreased gene expression of cytokines of IL-4, IFN-γ, interleukin (IL)-1β and cyclooxygenase (COX)-2 in BPA-stimulated HMC-1 cells. Hence, we speculate that CTB glycoprotein can use as a potent anti-inflammatory agent for inflammatory allergic diseases.


CTB glycoprotein IL-4 IFN-γ IL-1β inflammation HMC-1 cells bisphenol A 



This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund; KRF-2008-521-C00167).


  1. 1.
    Kolpin, D. W., E. T. Furlong, M. T. Meyer, E. M. Thurman, S. D. Zaugg, L. B. Barber, et al. 2002. Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999–2000: a national reconnaissance. Environ. Sci. Technol. 36:1202–1211. doi: 10.1021/es011055j.PubMedCrossRefGoogle Scholar
  2. 2.
    Wozniak, A. L., N. N. Bulayeva, and C. S. Watson,. 2005. Xenoestrogens at picomolar to nanomolar concentrations trigger membrane estrogen receptor-alpha-mediated Ca2+ fluxes and prolactin release in GH3/B6 pituitary tumor cells. Environ. Health Perspect. 113:431–439.PubMedCrossRefGoogle Scholar
  3. 3.
    Veldhoen, N., R. C. Skirrow, H. Osachoff, H. Wigmore, D. J. Clapson, M. P. Gunderson, et al. 2006. The bactericidal agent triclosan modulates thyroid hormone-associated gene expression and disrupts postembryonic anuran development. Aquat. Toxicol. 80:217–227. doi: 10.1016/j.aquatox.2006.08.010.PubMedCrossRefGoogle Scholar
  4. 4.
    Alonso-Magdalena, P., O. Laribi, A. B. Ropero, E. Fuentes, C. Ripoll, B. Soria, et al. 2005. Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans. Environ. Health Perspect. 113:969–977.PubMedGoogle Scholar
  5. 5.
    Masuno, H., J. Iwanami, T. Kidani, K. Sakayama, and K. Honda, . 2005. Bisphenol A accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway. Toxicol. Sci. 84:319–327. doi: 10.1093/toxsci/kfi088.PubMedCrossRefGoogle Scholar
  6. 6.
    Marshall, J. S. 2004. Mast cell responses to pathogens. Nat. Rev. Immunol. 4:787–799. doi: 10.1038/nri1460.PubMedCrossRefGoogle Scholar
  7. 7.
    Rivera, J., and A. M. Gilfillan,. 2006. Molecular regulation of mast cell activation. J. Allergy Clin. Immunol. 117:1214–1225. doi: 10.1016/j.jaci.2006.04.015.PubMedCrossRefGoogle Scholar
  8. 8.
    Kawata, R., S. T. Reddy, B. Wolner, and H. R. Herschman,. 1995. Prostaglandin synthase 1 and prostaglandin synthase 2 both participate in activation-induced prostaglandin D2 production in mast cells. J. Immunol. 155:818–825.PubMedGoogle Scholar
  9. 9.
    Moon, T. C., M. Murakami, M. D. Ashraf, I. Kudo, and H. W. Chang,. 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: 10.1006/cimm.1998.1284.PubMedCrossRefGoogle Scholar
  10. 10.
    Swindle, E. J., and D. D. Metcalfe,. 2007. The role of reactive oxygen species and nitric oxide in mast cell-dependent inflammatory processes. Immunol. Rev. 217:186–205. doi: 10.1111/j.1600-065X.2007.00513.x.PubMedCrossRefGoogle Scholar
  11. 11.
    Cobb, M. H., and E. J. Goldsmith,. 2000. Dimerization in MAP-kinase signaling. Trends Biochem. Sci. 25:7–9. doi: 10.1016/S0968-0004(99)01508-X.PubMedCrossRefGoogle Scholar
  12. 12.
    Davis, R. J. 1993. The mitogen-activated protein kinase signal transduction pathway. J. Biol. Chem. 268:14553–14556.PubMedGoogle Scholar
  13. 13.
    Nishida, E., and Y. Gotoh,. 1993. The MAPK cascade is essential for diverse signal transduction pathways. Trends Biochem. Sci. 18:128–131. doi: 10.1016/0968-0004(93)90019-J.PubMedCrossRefGoogle Scholar
  14. 14.
    Cobb, M. H., and E. J. Goldsmith,. 1995. How MAPK are regulated. J. Biol. Chem. 270:14843–14846. doi: 10.1074/jbc.270.25.14843.PubMedCrossRefGoogle Scholar
  15. 15.
    Ahamed, J., R. T. Venkatesha, E. B. Thangam, and H. Ali,. 2004. C3a enhances nerve growth factor-induced NFAT activation and chemokine production in a human mast cell line, HMC-1. J. Immunol. 172:6961–6968.PubMedGoogle Scholar
  16. 16.
    Kyriakis, J., and M. Avruch,. 1996. Sounding the alarm: protein kinase cascades activated by stress and inflammation. J. Biol. Chem. 271:24313–24316. doi: 10.1074/jbc.271.40.24313.PubMedCrossRefGoogle Scholar
  17. 17.
    Lu, H. T., D. D. Yang, M. Wysk, E. Gatti, I. Mellman, R. J. Davis, and R. A. Flavell,. 1999. Defective IL-12 production in mitogen-activated protein (MAP) kinase kinase 3 (Mkk3)-deficient mice. EMBO J. 18:1845–1857. doi: 10.1093/emboj/18.7.1845.PubMedCrossRefGoogle Scholar
  18. 18.
    Lee, Y. N., J. Tuckerman, H. Nechushtan, G. Schutz, E. Razin, and P. Angel,. 2004. c-Fos as a regulator of degranulation and cytokine production in FcepsilonRI-activated mast cells. J. Immunol. 173:2571–2577.PubMedGoogle Scholar
  19. 19.
    Shaulian, E., and M. Karin,. 2002. AP-1 as a regulator of cell life and death. Nat. Cell Biol. 4:131–136. doi: 10.1038/ncb0502-e131.CrossRefGoogle Scholar
  20. 20.
    Chandel, N. S., W. C. Trzyna, D. S. McClintock, and P. T. Schumacker,. 2000. Role of oxidants in NF-kappa B activation and TNF-alpha gene transcription induced by hypoxia and endotoxin. J. Immunol. 165:1013–1021.PubMedGoogle Scholar
  21. 21.
    Bochenek, G., E. Nizankowska, A. Gielicz, M. Swierczynska, and A. Szczeklik,. 2004. Plasma 9alpha,11beta-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma. Thorax 59:459–464. doi: 10.1136/thx.2003.013573.PubMedCrossRefGoogle Scholar
  22. 22.
    Lee, S. J., and K. T. Lim,. 2005. Apoptosis induced by glycoprotein (150-kDa) isolated from Solanum nigrum L. is not related to intracellular reactive oxygen species (ROS) in HCT-116 cells. Cancer Chemother. Pharmacol. 57:507–516. doi: 10.1007/s00280-005-0045-0.PubMedCrossRefGoogle Scholar
  23. 23.
    Lee, S. J., P. S. Oh, and K. T. Lim,. 2006. Hepatoprotective and hypolipidaemic effects of glycoprotein isolated from Gardenia jasminoides Ellis in mice. Clin. Exp. Pharmacol. Physiol. 33:925–933. doi: 10.1111/j.1440-1681.2006.04466.x.PubMedCrossRefGoogle Scholar
  24. 24.
    Oh, P. S., S. J. Lee, and K. T. Lim,. 2007. Glycoprotein isolated from Rhus verniciflua stokes inhibits inflammation-related protein and nitric oxide production in LPS-stimulated RAW 264.7 cells. Biol. Pharm. Bull. 30:111–116. doi: 10.1248/bpb.30.111.PubMedCrossRefGoogle Scholar
  25. 25.
    Lee, I. K., C. J. Kim, K. S. Song, H. M. Kim, H. Koshino, M. Uramoto, and I. D. Yoo,. 1996. Cytotoxic benzyl dihydroflavonols from Cudrania tricuspidata. Phytochemistry 41:213–216. doi: 10.1016/0031-9422(95)00609-5.PubMedCrossRefGoogle Scholar
  26. 26.
    Hwang, J. H., S. S. Hong, X. H. Han, J. S. Hwang, D. H. Lee, H. S. Lee, Y. P. Yun, Y. S. Kim, J. S. Ro, and B. Y. Hwang,. 2007. Prenylated xanthones from the root bark of Cudrania tricuspidata. J. Nat. Prod. 70:1207–1209. doi: 10.1021/np070059k.PubMedCrossRefGoogle Scholar
  27. 27.
    Joo, H. Y., and K. T. Lim,. 2009. Glycoprotein isolated from Cudrania tricuspidata Bureau inhibits iNO and COX-2 expression through modulation of NF-κB in LPS-stimulated RAW264.7 cells. Environ. Toxicol. Pharmacol. 27:247–252. doi: 10.1016/j.etap.2008.10.014.CrossRefGoogle Scholar
  28. 28.
    Neville, D. M., and H. Glossmann,. 1974. Molecular weight determination of membrane protein and glycoprotein subunits by discontinuous gel electrophoresis in dodecyl sulfate. Methods Enzymol. 32:92–102. doi: 10.1016/0076-6879(74)32012-5.PubMedCrossRefGoogle Scholar
  29. 29.
    Shore, P. A., A. Brukhalter, and V. H. Cohn, Jr. 1959. A method for the fluorometric assay of histamine in tissues. J. Pharmacol. Exp. Ther. 127:182–186.PubMedGoogle Scholar
  30. 30.
    Kemp, S. F., and R. F. Lockey,. 2002. Anaphylaxis: a review of causes and mechanisms. J. Allergy Clin. Immunol. 110:341–348. doi: 10.1067/mai.2002.126811.PubMedCrossRefGoogle Scholar
  31. 31.
    Metzger, H., G. Alcaraz, R. Hohman, J. P. Kinet, V. Pribluda, and R. Quarto,. 1986. The receptor with high affinity for immunoglobulin E. Annu. Rev. Immunol. 4:419–470. doi: 10.1146/annurev.iy.04.040186.002223.PubMedCrossRefGoogle Scholar
  32. 32.
    Mekori, Y. A., and D. D. Metcalfe,. 2000. Mast cells in innate immunity. Immunol. Rev. 173:131–140. doi: 10.1034/j.1600-065X.2000.917305.x.PubMedCrossRefGoogle Scholar
  33. 33.
    Galli, S. J., J. Kalesnikoff, M. A. Grimbaldeston, A. M. Piliponsky, C. M. Williams, and M. Tsai,. 2005. Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu. Rev. Immunol. 23:749–786. doi: 10.1146/annurev.immunol.21.120601.141025.PubMedCrossRefGoogle Scholar
  34. 34.
    Walls, A. F., S. H. He, M. G. Buckley, and A. R. McEuen,. 2001. Roles of the mast cell and basophil in asthma. Clin. Exp. Allergy Rev. 1:68–72. doi: 10.1046/j.1472-9725.2001.00009.x.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Molecular Biochemistry Laboratory, Biotechnology Research InstituteChonnam National UniversityGwangju CitySouth Korea

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