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Impact on Inflammation and Recovery of Skin Barrier by Nordihydroguaiaretic Acid as a Protease-Activated Receptor 2 Antagonist

  • Kim, Hyo-Young (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University) ;
  • Goo, Jung-Hyun (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University) ;
  • Joo, Yeon-Ah (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University) ;
  • Lee, Ha-Yoen (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University) ;
  • Lee, Se-Mi (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University) ;
  • Oh, Chang-Taek (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University) ;
  • Ahn, Soo-Mi (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University) ;
  • Kim, Nam-Hoon (Sehwa High School) ;
  • Hwang, Jae-Sung (Department of Genetic Engineering, College of Life Science and Skin Biotechnology Center, Kyung Hee University)
  • Received : 2012.06.11
  • Accepted : 2012.07.17
  • Published : 2012.09.30

Abstract

Atopic dermatitis is a chronic, inflammatory disease of the skin with increased transepidermal water loss. Both an abnormal inflammatory response and a defective skin barrier are known to be involved in the pathogenesis of atopic dermatitis. Protease activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is activated by both trypsin and a specific agonist peptide, SLIGKV-$NH_2$. PAR2 is expressed in suprabasal layers of the epidermis and regulates inflammatory responses and barrier homeostasis. In this study, we show that nordihydroguaiaretic acid (NDGA) inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular $Ca^{2+}$ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine and intercellular cell adhesion molecule-1 in HaCaT keratinocytes. Also, NDGA decreases the protein expression of involucrin, a differentiation maker of keratinocyte, in both HaCaT keratinocytes and normal human epidermal keratinocytes. We examined NDGA-recovered skin barrier in atopic dermatitis by using an oxazolone-induced atopic dermatitis model in hairless mice. Topical application of NDGA produced an increase in transepidermal water loss recovery and a decrease in serum IgE level, without weight loss. Accordingly, we suggest that NDGA acts as a PAR2 antagonist and may be a possible therapeutic agent for atopic dermatitis.

Keywords

References

  1. Bohm, S. K., Kong, W., Bromme, D., Smeekens, S. P., Anderson, D. C., Connolly, A., Kahn, M., Nelken, N. A., Coughlin, S. R., Payan, D. G. and Bunnett, N. W. (1996) Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2. Biochem. J. 314, 1009-1016. https://doi.org/10.1042/bj3141009
  2. Buddenkotte, J., Stroh, C., Engels, I. H., Moormann, C., Shpacovitch, V. M., Seeliger, S., Vergnolle, N., Vestweber, D., Luger, T. A., Schulze-Osthoff, K. and Steinhoff, M. (2005) Agonists of proteinase-activated receptor-2 stimulate upregulation of intercellular cell adhesion molecule-1 in primary human keratinocytes via activation of NF-kappa B. J. Invest. Dermatol. 124, 38-45. https://doi.org/10.1111/j.0022-202X.2004.23539.x
  3. Demerjian, M., Hachem, J. P., Tschachler, E., Denecker, G., Declercq, W., Vandenabeele, P., Mauro, T., Hupe, M., Crumrine, D., Roelandt, T., Houben, E., Elias, P. M. and Feingold, K. R. (2008) Acute modulations in permeability barrier function regulate epidermal cornification: role of caspase-14 and the protease-activated receptor type 2. Am. J. Pathol. 172, 86-97. https://doi.org/10.2353/ajpath.2008.070161
  4. Eads, D., Hansen, R., Oyegunwa, A., Cecil, C., Culver, C., Scholle, F., Petty, I. and Laster, S. (2009) Terameprocol, a methylated derivative of nordihydroguaiaretic acid, inhibits production of prostaglandins and several key inflammatory cytokines and chemokines. J. Inflamm (Lond). 6, 2. https://doi.org/10.1186/1476-9255-6-2
  5. Elias, P. M. and Steinhoff, M. (2008) "Outside-to-inside" (and now back to "outside") pathogenic mechanisms in atopic dermatitis. J. Invest. Dermatol. 128, 1067-1070. https://doi.org/10.1038/jid.2008.88
  6. Frateschi, S., Camerer, E., Crisante, G., Rieser, S., Membrez, M., Charles, R. P., Beermann, F., Stehle, J. C., Breiden, B., Sandhoff, K., Rotman, S., Haftek, M., Wilson, A., Ryser, S., Steinhoff, M., Coughlin, S. R. and Hummler, E. (2011) PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin. Nat. Commun. 2, 161. https://doi.org/10.1038/ncomms1162
  7. Grant, A. D., Cottrell, G. S., Amadesi, S., Trevisani, M., Nicoletti, P., Materazzi, S., Altier, C., Cenac, N., Zamponi, G. W., Bautista-Cruz, F., Lopez, C. B., Joseph, E. K., Levine, J. D., Liedtke, W., Vanner, S., Vergnolle, N., Geppetti, P. and Bunnett, N. W. (2007) Protease-activated receptor 2 sensitizes the transient receptor potential vanilloid 4 ion channel to cause mechanical hyperalgesia in mice. J. Physiol. (Lond). 578, 715-733. https://doi.org/10.1113/jphysiol.2006.121111
  8. Hachem, J. P., Houben, E., Crumrine, D., Man, M. Q., Schurer, N., Roelandt, T., Choi, E. H., Uchida, Y., Brown, B. E., Feingold, K. R. and Elias, P. M. (2006) Serine protease signaling of epidermal permeability barrier homeostasis. J. Invest. Dermatol. 126, 2074-2086. https://doi.org/10.1038/sj.jid.5700351
  9. He, S., Aslam, A., Gaça, M. D., He, Y., Buckley, M. G., Hollenberg, M. D. and Walls, A. F. (2004) Inhibitors of tryptase as mast cell-stabilizing agents in the human airways: effects of tryptase and other agonists of proteinase-activated receptor 2 on histamine release. J. Pharmacol. Exp. Ther. 309, 119-126. https://doi.org/10.1124/jpet.103.061291
  10. Hou, L., Kapas, S., Cruchley, A. T., Macey, M. G., Harriott, P., Chinni, C., Stone, S. R. and Howells, G. L. (1998) Immunolocalization of protease-activated receptor-2 in skin: receptor activation stimulates interleukin-8 secretion by keratinocytes in vitro. Immunology 94, 356-362. https://doi.org/10.1046/j.1365-2567.1998.00528.x
  11. Jeong, S. K., Kim, H. J., Youm, J. K., Ahn, S. K., Choi, E. H., Sohn, M. H., Kim, K. E., Hong, J. H., Shin, D. M. and Lee, S. H. (2008) Mite and cockroach allergens activate protease-activated receptor 2 and delay epidermal permeability barrier recovery. J. Invest. Dermatol. 128, 1930-1939. https://doi.org/10.1038/jid.2008.13
  12. Jin, H., He, R., Oyoshi, M. and Geha, R. S. (2009) Animal models of atopic dermatitis. J. Invest. Dermatol. 129, 31-40. https://doi.org/10.1038/jid.2008.106
  13. Kang, J. S., Yoon, W. K., Han, M. H., Lee, H., Lee, C. W., Lee, K. H., Han, S. B., Lee, K., Yang, K. H., Park, S. K. and Kim, H. M. (2008) Inhibition of atopic dermatitis by topical application of silymarin in NC/Nga mice. Int. Immunopharmacol. 8, 1475-1480. https://doi.org/10.1016/j.intimp.2008.06.004
  14. Lee, S. E., Kim, J. M., Jeong, S. K., Jeon, J. E., Yoon, H. J., Jeong, M. K. and Lee, S. H. (2010) Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes. Arch. Dermatol. Res. 302, 745-756. https://doi.org/10.1007/s00403-010-1074-z
  15. Mahajan, U. M., Gupta, C., Wagh, P. R., Karpe, P. A. and Tikoo, K. (2011) Alteration in inflammatory/apoptotic pathway and histone modifications by nordihydroguaiaretic acid prevents acute pancreatitis in swiss albino mice. Apoptosis 16, 1138-1149. https://doi.org/10.1007/s10495-011-0643-8
  16. Man, M. Q., Hatano, Y., Lee, S. H., Man, M., Chang, S., Feingold, K. R., Leung, D. Y, Holleran, W., Uchida, Y. and Elias, P. M. (2008) Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges. J. Invest. Dermatol. 128, 79-86. https://doi.org/10.1038/sj.jid.5701011
  17. Nystedt, S., Ramakrishnan, V. and Sundelin, J. (1996) The proteinase-activated receptor 2 is induced by inflammatory mediators in human endothelial cells. Comparison with the thrombin receptor. J. Biol. Chem. 271, 14910-14915. https://doi.org/10.1074/jbc.271.25.14910
  18. Rahman, S., Ansari, R. A., Rehman, H., Parvez, S. and Raisuddin, S. (2011) Nordihydroguaiaretic acid from creosote bush (Larrea tridentata) mitigates 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory and oxidative stress responses of tumor promotion cascade in mouse skin. Evid. Based Complement Alternat. Med. 2011, 734785.
  19. Roelandt, T., Heughebaert, C., Verween, G., Giddelo, C., Verbeken, G., Pirnay, J. P., Devos, D., Crumrine, D., Roseeuw, D., Elias, P. M. and Hachem, J. P. (2011) Actin dynamics regulate immediate PAR-2-dependent responses to acute epidermal permeability barrier abrogation. J. Dermatol. Sci. 61, 101-109. https://doi.org/10.1016/j.jdermsci.2010.11.016
  20. Steven, A. C. and Steinert, P. M. (1994) Protein composition of cornified cell envelopes of epidermal keratinocytes. J. Cell Sci. 107, 693-700.
  21. Tsujii, K., Andoh, T., Ui, H., Lee, J. B. and Kuraishi, Y. (2009) Involvement of tryptase and proteinase-activated receptor-2 in spontaneous itch-associated response in mice with atopy-like dermatitis. J. Pharmacol. Sci. 109, 388-395. https://doi.org/10.1254/jphs.08332FP
  22. Vergnolle, N., Hollenberg, M. D., Sharkey, K. A. and Wallace, J. L. (1999) Characterization of the inflammatory response to proteinase-activated receptor-2 (PAR2)-activating peptides in the rat paw. Br. J. Pharmacol. 127, 1083-1090. https://doi.org/10.1038/sj.bjp.0702634
  23. Vergnolle, N., Macnaughton, W. K., Al-Ani, B., Saifeddine, M., Wallace, J. L. and Hollenberg, M. D. (1998) Proteinase-activated receptor 2 (PAR2)-activating peptides: identification of a receptor distinct from PAR2 that regulates intestinal transport. Proc. Natl. Acad. Sci. USA 95, 7766-7771. https://doi.org/10.1073/pnas.95.13.7766
  24. Yun, J. W., Seo, J. A., Jeong, Y. S., Bae, I. H., Jang, W. H., Lee, J., Kim, S. Y., Shin, S. S., Woo, B. Y., Lee, K. W., Lim, K. M. and Park, Y. H. (2011) TRPV1 antagonist can suppress the atopic dermatitis-like symptoms by accelerating skin barrier recovery. J. Dermatol. Sci. 62, 8-15.

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