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Polyphenon-60 displays a therapeutic effect on acne by suppression of TLR2 and IL-8 expression via down-regulating the ERK1/2 pathway

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Abstract

Propionibacterium acnes (P. acnes) is a well-known acne-inducing factor which causes inflammatory skin lesions by enhancing cytokine production through toll-like receptor 2 (TLR2). Green tea extract catechin has been documented to possess anti-inflammatory effects. However, little is known about the mechanisms involved or any direct effect of green tea catechin on acne. The present study investigated the therapeutic effects and mechanism of polyphenon-60, also known as green tea catechin compound, on acne in vitro and in vivo. In a clinical study using topical polyphenon-60 treatment, acne patients showed symptomatic improvement with decrease in the number of comedos and pustules. To investigate the mechanism underlying the activity of polyphenon-60 in acne therapy, an in vitro study was performed. We found that polyphenon-60 reduced the levels of P. acnes-enhanced TLR2 and interleukin-8 (IL-8) in THP-1 cells, human monocyte cell line and human primary monocytes. Taken together, these data demonstrate that polyphenon-60 has a therapeutic effect on acne by suppressing inflammation, specifically by inhibiting TLR2 expression and IL-8 secretion via down-regulation of extracellular signal-regulated kinases 1/2 (ERK1/2) pathway and activator protein-1 (AP-1) pathway.

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References

  1. Alestas T, Ganceviciene R, Fimmel S, Muller-Decker K, Zouboulis CC (2006) Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med 84(1):75–87

    Article  PubMed  CAS  Google Scholar 

  2. Augustin K, Frank J, Augustin S, Langguth P, Ohrvik V, Witthoft CM, Rimbach G, Wolffram S (2009) Green tea extracts lower serum folates in rats at very high dietary concentrations only and do not affect plasma folates in a human pilot study. J Physiol Pharmacol 60(3):103–108

    PubMed  CAS  Google Scholar 

  3. Ayangco L, Sheridan PJ (2003) Minocycline-induced staining of torus palatinus and alveolar bone. J Periodontol 74(5):669–671

    Article  PubMed  Google Scholar 

  4. Boehme SA, Sullivan SK, Crowe PD, Santos M, Conlon PJ, Sriramarao P, Bacon KB (1999) Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration. J Immunol 163(3):1611–1618

    PubMed  CAS  Google Scholar 

  5. Chacko SM, Thambi PT, Kuttan R, Nishigaki I (2010) Beneficial effects of green tea: a literature review. Chin Med 5:13

    Article  PubMed  Google Scholar 

  6. Chen Q, Koga T, Uchi H, Hara H, Terao H, Moroi Y, Urabe K, Furue M (2002) Propionibacterium acnes-induced IL-8 production may be mediated by NF-kappaB activation in human monocytes. J Dermatol Sci 29(2):97–103

    Article  PubMed  CAS  Google Scholar 

  7. Claret FX, Hibi M, Dhut S, Toda T, Karin M (1996) A new group of conserved coactivators that increase the specificity of AP-1 transcription factors. Nature 383(6599):453–457

    Article  PubMed  CAS  Google Scholar 

  8. Georgel P, Crozat K, Lauth X, Makrantonaki E, Seltmann H, Sovath S, Hoebe K, Du X, Rutschmann S, Jiang Z, Bigby T, Nizet V, Zouboulis CC, Beutler B (2005) A toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria. Infect Immun 73(8):4512–4521

    Article  PubMed  CAS  Google Scholar 

  9. Goulden V, Clark SM, Cunliffe WJ (1997) Post-adolescent acne: a review of clinical features. Br J Dermatol 136(1):66–70

    Article  PubMed  CAS  Google Scholar 

  10. Grange PA, Raingeaud J, Calvez V, Dupin N (2009) Nicotinamide inhibits Propionibacterium acnes-induced IL-8 production in keratinocytes through the NF-kappaB and MAPK pathways. J Dermatol Sci 56(2):106–112

    Article  PubMed  CAS  Google Scholar 

  11. Hess J, Angel P, Schorpp-Kistner M (2004) AP-1 subunits: quarrel and harmony among siblings. J Cell Sci 117(Pt 25):5965–5973

    Article  PubMed  CAS  Google Scholar 

  12. Hirao K, Yumoto H, Nakanishi T, Mukai K, Takahashi K, Takegawa D, Matsuo T (2010) Tea catechins reduce inflammatory reactions via mitogen-activated protein kinase pathways in toll-like receptor 2 ligand-stimulated dental pulp cells. Life Sci 86(17–18):654–660

    Article  PubMed  CAS  Google Scholar 

  13. Isard O, Leveque M, Knol AC, Aries MF, Khammari A, Nguyen JM, Castex-Rizzi N, Dreno B (2011) Anti-inflammatory properties of a new undecyl-rhamnoside (APRC11) against P. acnes. Arch Dermatol Res 303(10):707–713

    Article  PubMed  CAS  Google Scholar 

  14. Jugeau S, Tenaud I, Knol AC, Jarrousse V, Quereux G, Khammari A, Dreno B (2005) Induction of toll-like receptors by Propionibacterium acnes. Br J Dermatol 153(6):1105–1113

    Article  PubMed  CAS  Google Scholar 

  15. Kampen GT, Stafford S, Adachi T, Jinquan T, Quan S, Grant JA, Skov PS, Poulsen LK, Alam R (2000) Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases. Blood 95(6):1911–1917

    PubMed  CAS  Google Scholar 

  16. Kang S, Cho S, Chung JH, Hammerberg C, Fisher GJ, Voorhees JJ (2005) Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo. Am J Pathol 166(6):1691–1699

    Article  PubMed  CAS  Google Scholar 

  17. Katiyar SK, Elmets CA (2001) Green tea polyphenolic antioxidants and skin photoprotection (review). Int J Oncol 18(6):1307–1313

    PubMed  CAS  Google Scholar 

  18. Katiyar SK, Matsui MS, Elmets CA, Mukhtar H (1999) Polyphenolic antioxidant (−)-epigallocatechin-3-gallate from green tea reduces UVB-induced inflammatory responses and infiltration of leukocytes in human skin. Photochem Photobiol 69(2):148–153

    PubMed  CAS  Google Scholar 

  19. Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, Brightbill HD, Holland D, Cunliffe WJ, Akira S, Sieling PA, Godowski PJ, Modlin RL (2002) Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol 169(3):1535–1541

    PubMed  CAS  Google Scholar 

  20. Kinney MA, Yentzer BA, Fleischer AB Jr, Feldman SR (2010) Trends in the treatment of acne vulgaris: are measures being taken to avoid antimicrobial resistance? J Drugs Dermatol 9(5):519–524

    PubMed  Google Scholar 

  21. Kurokawa I, Danby FW, Ju Q, Wang X, Xiang LF, Xia L, Chen W, Nagy I, Picardo M, Suh DH, Ganceviciene R, Schagen S, Tsatsou F, Zouboulis CC (2009) New developments in our understanding of acne pathogenesis and treatment. Exp Dermatol 18(10):821–832

    Article  PubMed  CAS  Google Scholar 

  22. Labro MT (1993) Immunomodulation by antibacterial agents. Is it clinically relevant? Drugs 45(3):319–328

    Article  PubMed  CAS  Google Scholar 

  23. Lee JH, Shim JS, Chung MS, Lim ST, Kim KH (2009) In vitro anti-adhesive activity of green tea extract against pathogen adhesion. Phytother Res 23(4):460–466

    Article  PubMed  CAS  Google Scholar 

  24. Leyden JJ, McGinley KJ, Mills OH, Kligman AM (1975) Age-related changes in the resident bacterial flora of the human face. J Invest Dermatol 65(4):379–381

    Article  PubMed  CAS  Google Scholar 

  25. Leyden JJ, McGinley KJ, Mills OH, Kligman AM (1975) Propionibacterium levels in patients with and without acne vulgaris. J Invest Dermatol 65(4):382–384

    Article  PubMed  CAS  Google Scholar 

  26. Lu G, Liao J, Yang G, Reuhl KR, Hao X, Yang CS (2006) Inhibition of adenoma progression to adenocarcinoma in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model in A/J mice by tea polyphenols and caffeine. Cancer Res 66(23):11494–11501

    Article  PubMed  CAS  Google Scholar 

  27. Lyte P, Sur R, Nigam A, Southall MD (2009) Heat-killed Propionibacterium acnes is capable of inducing inflammatory responses in skin. Exp Dermatol 18(12):1070–1072

    Article  PubMed  CAS  Google Scholar 

  28. Marotte H, Ruth JH, Campbell PL, Koch AE, Ahmed S (2010) Green tea extract inhibits chemokine production, but up-regulates chemokine receptor expression, in rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis. Rheumatology (Oxford) 49(3):467–479

    Article  CAS  Google Scholar 

  29. McInturff JE, Modlin RL, Kim J (2005) The role of toll-like receptors in the pathogenesis and treatment of dermatological disease. J Invest Dermatol 125(1):1–8

    Article  PubMed  CAS  Google Scholar 

  30. McInturff JE, Wang SJ, Machleidt T, Lin TR, Oren A, Hertz CJ, Krutzik SR, Hart S, Zeh K, Anderson DH, Gallo RL, Modlin RL, Kim J (2005) Granulysin-derived peptides demonstrate antimicrobial and anti-inflammatory effects against Propionibacterium acnes. J Invest Dermatol 125(2):256–263

    PubMed  CAS  Google Scholar 

  31. Medzhitov R, Preston-Hurlburt P, Janeway CA Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388(6640):394–397

    Article  PubMed  CAS  Google Scholar 

  32. Nagy I, Pivarcsi A, Koreck A, Szell M, Urban E, Kemeny L (2005) Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Invest Dermatol 124(5):931–938

    Article  PubMed  CAS  Google Scholar 

  33. Nakatsuji T, Kao MC, Fang JY, Zouboulis CC, Zhang L, Gallo RL, Huang CM (2009) Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. J Invest Dermatol 129(10):2480–2488

    Article  PubMed  CAS  Google Scholar 

  34. Nakatsuji T, Liu YT, Huang CP, Zoubouis CC, Gallo RL, Huang CM (2008) Antibodies elicited by inactivated propionibacterium acnes-based vaccines exert protective immunity and attenuate the IL-8 production in human sebocytes: relevance to therapy for acne vulgaris. J Invest Dermatol 128(10):2451–2457

    Article  PubMed  CAS  Google Scholar 

  35. Philips BJ, Coyle CH, Morrisroe SN, Chancellor MB, Yoshimura N (2009) Induction of apoptosis in human bladder cancer cells by green tea catechins. Biomed Res 30(4):207–215

    Article  PubMed  CAS  Google Scholar 

  36. Ramakrishna J, Johnson AR, Banner BF (2009) Long-term minocycline use for acne in healthy adolescents can cause severe autoimmune hepatitis. J Clin Gastroenterol 43(8):787–790

    Article  PubMed  Google Scholar 

  37. Rice-Evans CA, Miller NJ, Bolwell PG, Bramley PM, Pridham JB (1995) The relative antioxidant activities of plant-derived polyphenolic flavonoids. Free Radic Res 22(4):375–383

    Article  PubMed  CAS  Google Scholar 

  38. Scharf S, Hippenstiel S, Flieger A, Suttorp N, N’Guessan PD (2010) Induction of human beta-defensin-2 in pulmonary epithelial cells by Legionella pneumophila: involvement of TLR2 and TLR5, p38 MAPK, JNK, NF-kappaB, and AP-1. Am J Physiol Lung Cell Mol Physiol 298(5):L687–L695

    Article  PubMed  CAS  Google Scholar 

  39. Shibata M, Katsuyama M, Onodera T, Ehama R, Hosoi J, Tagami H (2009) Glucocorticoids enhance Toll-like receptor 2 expression in human keratinocytes stimulated with Propionibacterium acnes or proinflammatory cytokines. J Invest Dermatol 129(2):375–382

    Article  PubMed  CAS  Google Scholar 

  40. Smith TM, Gilliland K, Clawson GA, Thiboutot D (2008) IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway. J Invest Dermatol 128(5):1286–1293

    Article  PubMed  CAS  Google Scholar 

  41. Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G (1998) Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells. J Exp Med 188(9):1751–1756

    Article  PubMed  CAS  Google Scholar 

  42. Vijaya K, Ananthan S, Nalini R (1995) Antibacterial effect of theaflavin, polyphenon 60 (Camellia sinensis) and Euphorbia hirta on Shigella spp.—a cell culture study. J Ethnopharmacol 49(2):115–118

    Article  PubMed  CAS  Google Scholar 

  43. Vowels BR, Yang S, Leyden JJ (1995) Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne. Infect Immun 63(8):3158–3165

    PubMed  CAS  Google Scholar 

  44. Whitmarsh AJ, Davis RJ (1996) Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med (Berl) 74(10):589–607

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported the Ministry of Knowledge Economy [a Grant No. 10033778 (2009)].

Conflict of interest

All coauthors do not have any financial conflicts of interest or commercial considerations concerning these findings.

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Authors and Affiliations

  1. Department of Life Science, SIS Immunology Research Center, Sookmyung Women’s University, Seoul, 140-742, Korea

    Min Kyung Jung, Soogyeong Ha & Daeho Cho

  2. Biotech. Team, Cent’l Res. Inst., Ilyang Pharm., Co., Ltd., 359, giheung-gu, Yongin-si, Gyeonggi-do, 449-726, Korea

    Ju-ah Son & Ji Hye Song

  3. Department of Animal Biotechnology, Konkuk University, 1, Seoul, 140-731, Korea

    Younkyung Houh

  4. Department of Dermatology, Yeouido St. Mary’s Hospital, The Catholic University of Korea, Seoul, 150-713, Korea

    Eujin Cho, Ji Hoon Chun & Hyun Jeong Park

  5. Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 305-806, Korea

    Suk Ran Yoon

  6. Department of Plastic Surgery, College of Medicine, Sungkyunkwan University, Seoul, 110-745, Korea

    Yoolhee Yang & Sa Ik Bang

  7. Department of B.Sc. kinesiology, McGill University, Montreal, QC, H3A 3R1, Canada

    Minjung Kim

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  1. Min Kyung Jung
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Correspondence to Hyun Jeong Park or Daeho Cho.

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M. K. Jung and S. Ha contributed equally to this work.

Corresponding authors D. Cho and H. J. Park contributed equally to this work.

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Jung, M.K., Ha, S., Son, Ja. et al. Polyphenon-60 displays a therapeutic effect on acne by suppression of TLR2 and IL-8 expression via down-regulating the ERK1/2 pathway. Arch Dermatol Res 304, 655–663 (2012). https://doi.org/10.1007/s00403-012-1249-x

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