Amino Acids

, Volume 42, Issue 6, pp 2513–2519 | Cite as

Epigallocatechin-3-O-gallate inhibits the production of thymic stromal lymphopoietin by the blockade of caspase-1/NF-κB pathway in mast cells

  • Phil-Dong Moon
  • In-Hwa Choi
  • Hyung-Min Kim
Short Communication


The cytokine thymic stromal lymphopoietin (TSLP) has been implicated in the development and progression of allergic diseases such as atopic dermatitis, asthma, and chronic obstructive pulmonary disease. However, it has not yet been clarified the effect of epigallocatechin-3-O-gallate (EGCG) on the production of TSLP. Thus, we investigated how EGCG inhibits the production of TSLP in the human mast cell line (HMC-1) cells. Enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction, luciferase assay, and Western blot analysis were used to investigate the effects of EGCG. EGCG inhibited the production and mRNA expression of TSLP in HMC-1 cells. EGCG also inhibited the nuclear factor-κB luciferase activity induced by phorbol myristate acetate plus A23187. Furthermore, EGCG inhibited the activation of caspase-1 in HMC-1 cells. These results provide evidence that EGCG can help us to treat inflammatory and atopic diseases through the inhibition of TSLP.


Thymic stromal lymphopoietin Epigallocatechin-3-O-gallate Nuclear factor-κB Caspase-1 



Atopic dermatitis




Nuclear factor-κB


Phorbol myristate acetate


Thymic stromal lymphopoietin



This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0005591) and by a grant from the Kyung Hee University in 2011 (KHU-20110092).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abboud PA, Hake PW, Burroughs TJ, Odoms K, O’Connor M, Mangeshkar P, Wong HR, Zingarelli B (2008) Therapeutic effect of epigallocatechin-3-gallate in a mouse model of colitis. Eur J Pharmacol 579:411–417PubMedCrossRefGoogle Scholar
  2. Ahmed S, Marotte H, Kwan K, Ruth JH, Campbell PL, Rabquer BJ, Pakozdi A, Koch AE (2008) Epigallocatechin-3-gallate inhibits IL-6 synthesis and suppresses trans signaling by enhancing soluble gp130 production. Proc Natl Acad Sci USA 105:14692–14697PubMedCrossRefGoogle Scholar
  3. Boost KA, Hoegl S, Hofstetter C, Flondor M, Stegewerth K, Platacis I, Pfeilschifter J, Muhl H, Zwissler B (2007) Targeting caspase-1 by inhalation-therapy: effects of Ac-YVAD-CHO on IL-1 beta, IL-18 and downstream proinflammatory parameters as detected in rat endotoxaemia. Intensive Care Med 33:863–871PubMedCrossRefGoogle Scholar
  4. Dumortier A, Durham AD, Di Piazza M, Vauclair S, Koch U, Ferrand G, Ferrero I, Demehri S, Song LL, Farr AG, Leonard WJ, Kopan R, Miele L, Hohl D, Finke D, Radtke F (2010) Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin. PLoS One 5:e9258PubMedCrossRefGoogle Scholar
  5. Friend SL, Hosier S, Nelson A, Foxworthe D, Williams DE, Farr A (1994) A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells. Exp Hematol 22(3):321–328Google Scholar
  6. Gordon JR, Burd PR, Galli SJ (1990) Mast cells as a source of multifunctional cytokines. Immunol Today 11:458–464CrossRefGoogle Scholar
  7. Humke EW, Shriver SK, Starovasnik MA, Fairbrother WJ, Dixit VM (2000) ICEBERG: a novel inhibitor of interleukin-1beta generation. Cell 103:99–111PubMedCrossRefGoogle Scholar
  8. Kang JS, Yoon WK, Youm JK, Jeong SK, Park BD, Han MH, Lee H, Moon EY, Han SB, Lee CW, Lee K, Park SK, Yang KH, Kim HM (2008) Inhibition of atopic dermatitis-like skin lesions by topical application of a novel ceramide derivative, K6PC-9p, in NC/Nga mice. Exp Dermatol 17:958–964CrossRefGoogle Scholar
  9. Lamkanfi M, Kalai M, Saelens X, Declercq W, Vandenabeele P (2004) Caspase-1 activates nuclear factor of the kappa-enhancer in B cells independently of its enzymatic activity. J Biol Chem 279:24785–24793PubMedCrossRefGoogle Scholar
  10. Lamkanfi M, Kanneganti TD, Franchi L, Núñez G (2007) Caspase-1 inflammasomes in infection and inflammation. J Leukoc Biol 82:220–225PubMedCrossRefGoogle Scholar
  11. Lee HC, Ziegler SF (2007) Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in airway epithelial cells is controlled by NFkappaB. Proc Natl Acad Sci USA 104:914–919PubMedCrossRefGoogle Scholar
  12. Lee HC, Headley MB, Iseki M, Ikuta K, Ziegler SF (2008) Cutting edge: inhibition of NF-kappaB-mediated TSLP expression by retinoid X receptor. J Immunol 181:5189–5193PubMedGoogle Scholar
  13. Liu YJ (2006) Thymic stromal lymphopoietin: master switch for allergic inflammation. J Exp Med 203:269–273PubMedCrossRefGoogle Scholar
  14. Moon PD, Kim HM (2011) Thymic stromal lymphopoietin is expressed and produced by caspase-1/NF-κB pathway in mast cells. Cytokine 54:239–243PubMedCrossRefGoogle Scholar
  15. Morioka T, Yamanaka K, Mori H, Omoto Y, Tokime K, Kakeda M, Kurokawa I, Gabazza EC, Tsubura A, Yasutomi Y, Mizutani H (2009) IL-4/IL-13 antagonist DNA vaccination successfully suppresses Th2 type chronic dermatitis. Br J Dermatol 160:1172–1179PubMedCrossRefGoogle Scholar
  16. Oiwa M, Satoh T, Watanabe M, Niwa H, Hirai H, Nakamura M, Yokozeki H (2008) CRTH2-dependent, STAT6-independent induction of cedar pollen dermatitis. Clin Exp Allergy 38:1357–1366PubMedCrossRefGoogle Scholar
  17. Ozawa T, Koyama K, Ando T, Ohnuma Y, Hatsushika K, Ohba T, Sugiyama H, Hamada Y, Ogawa H, Okumura K, Nakao A (2007) Thymic stromal lymphopoietin secretion of synovial fibroblasts is positively and negatively regulated by Toll-like receptors/nuclear factor-kappaB pathway and interferon-gamma/dexamethasone. Mod Rheumatol 17:459–463PubMedCrossRefGoogle Scholar
  18. Plötz SG, Ring J (2010) What’s new in atopic eczema? Expert Opin Emerg Drugs 15:249–267PubMedCrossRefGoogle Scholar
  19. Quentmeier H, Drexler HG, Fleckenstein D, Zaborski M, Armstrong A, Sims JE, Lyman SD (2001) Cloning of human thymic stromal lymphopoietin (TSLP) and signaling mechanisms leading to proliferation. Leukemia 15:1286–1292PubMedCrossRefGoogle Scholar
  20. Rah DK, Han DW, Baek HS, Hyon SH, Park JC (2005) Prevention of reactive oxygen species-induced oxidative stress in human microvascular endothelial cells by green tea polyphenol. Toxicol Lett 155:269–275PubMedCrossRefGoogle Scholar
  21. Reefer AJ, Hulse KE, Lannigan JA, Solga MD, Wright PW, Kelly LA, Patrie J, Chapman MD, Woodfolk JA (2010) Flow cytometry imaging identifies rare T(H)2 cells expressing thymic stromal lymphopoietin receptor in a “proallergic” milieu. J Allergy Clin Immunol 126:105–1049 1058.e1–e10CrossRefGoogle Scholar
  22. Schneider C, Döcke WD, Zollner TM, Röse L (2009) Chronic mouse model of TMA-induced contact hypersensitivity. J Invest Dermatol 129:899–907PubMedCrossRefGoogle Scholar
  23. Schoonbroodt S, Legrand-Poels S, Best-Belpomme M, Piette J (1997) Activation of the NF-kappaB transcription factor in a T-lymphocytic cell line by hypochlorous acid. Biochem J 321:777–785Google Scholar
  24. Shan L, Redhu NS, Saleh A, Halayko AJ, Chakir J, Gounni AS (2010) Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemokines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2, p38, and JNK) and STAT3 pathways. J Immunol 184:7134–7143PubMedCrossRefGoogle Scholar
  25. Wheeler DS, Catravas JD, Odoms K, Denenberg A, Malhotra V, Wong HR (2004) Epigallocatechin-3-gallate, a green tea-derived polyphenol, inhibits IL-1 beta-dependent proinflammatory signal transduction in cultured respiratory epithelial cells. J Nutr 134:1039–1044PubMedGoogle Scholar
  26. Wu WH, Park CO, Oh SH, Kim HJ, Kwon YS, Bae BG, Noh JY, Lee KH (2010) Thymic stromal lymphopoietin-activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis. J Allergy Clin Immunol 126:290–299 299.e1–e4PubMedCrossRefGoogle Scholar
  27. Zhang Z, Hener P, Frossard N, Kato S, Metzger D, Li M, Chambon P (2009) Thymic stromal lymphopoietin overproduced by keratinocytes in mouse skin aggravates experimental asthma. Proc Natl Acad Sci USA 106:1536–1541PubMedCrossRefGoogle Scholar
  28. Zheng T, Oh MH, Oh SY, Schroeder JT, Glick AB, Zhu Z (2009) Transgenic expression of interleukin-13 in the skin induces a pruritic dermatitis and skin remodeling. J Invest Dermatol 129:742–751PubMedCrossRefGoogle Scholar
  29. Zheng Y, Morris A, Sunkara M, Layne J, Toborek M, Hennig B (2011) Epigallocatechin-gallate stimulates NF-E2-related factor and heme oxygenase-1 via caveolin-1 displacement. J Nutr Biochem (Epub ahead of print)Google Scholar
  30. Ziegler SF (2010) The role of thymic stromal lymphopoietin (TSLP) in allergic disorders. Curr Opin Immunol 22:795–799PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Pharmacology, College of Oriental MedicineInstitute of Oriental Medicine, Kyung Hee UniversitySeoulRepublic of Korea
  2. 2.Department of Oriental Dermatology, College of Oriental MedicineKyung Hee UniversitySeoulRepublic of Korea

Personalised recommendations