Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Dieckol, a Component of Ecklonia cava, Suppresses the Production of MDC/CCL22 via Down-Regulating STAT1 Pathway in Interferon-γ Stimulated HaCaT Human Keratinocytes

  • Kang, Na-Jin (Department of Biomedicine & Drug Development, School of Medicine, Jeju National University) ;
  • Koo, Dong-Hwan (Department of Biomedicine & Drug Development, School of Medicine, Jeju National University) ;
  • Kang, Gyeoung-Jin (Department of Medicine, School of Medicine, Jeju National University) ;
  • Han, Sang-Chul (Department of Medicine, School of Medicine, Jeju National University) ;
  • Lee, Bang-Won (Department of Medicine, School of Medicine, Jeju National University) ;
  • Koh, Young-Sang (Department of Biomedicine & Drug Development, School of Medicine, Jeju National University) ;
  • Hyun, Jin-Won (Department of Biomedicine & Drug Development, School of Medicine, Jeju National University) ;
  • Lee, Nam-Ho (Department of Chemistry, College of Natural Science, Jeju National University) ;
  • Ko, Mi-Hee (Jeju Biodiversity Research Institute) ;
  • Kang, Hee-Kyoung (Department of Biomedicine & Drug Development, School of Medicine, Jeju National University) ;
  • Yoo, Eun-Sook (Department of Biomedicine & Drug Development, School of Medicine, Jeju National University)
  • Received : 2014.12.15
  • Accepted : 2015.02.26
  • Published : 2015.05.01
Download PDF
⟨ Previous Next ⟩

Abstract

Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the inflammatory chemokines that controls the movement of monocytes, monocyte-derived dendritic cells, and natural killer cells. Serum and skin MDC/CCL22 levels are elevated in atopic dermatitis, which suggests that the chemokines produced from keratinocytes are responsible for attracting inflammatory lymphocytes to the skin. A major signaling pathway in the interferon-${\gamma}$ (IFN-${\gamma}$)-stimulated inflammation response involves the signal transducers and activators of transcription 1 (STAT1). In the present study, we investigated the anti-inflammatory effect of dieckol and its possible action mechanisms in the category of skin inflammation including atopic dermatitis. Dieckol inhibited MDC/CCL22 production induced by IFN-${\gamma}$ (10 ng/mL) in a dose dependent manner. Dieckol (5 and $10{\mu}M$) suppressed the phosphorylation and the nuclear translocation of STAT1. These results suggest that dieckol exhibits anti-inflammatory effect via the down-regulation of STAT1 activation.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea

References

  1. Baumer, W., Seegers, U., Braun, M., Tschernig, T. and Kietzmann, M. (2004) TARC and RANTES, but not CTACK, are induced in two models of allergic contact dermatitis. Effects of cilomilast and diflorasone diacetate on T-cell-attracting chemokines. Br. J. Dermatol. 151, 823-830. https://doi.org/10.1111/j.1365-2133.2004.06220.x
  2. Best, S. M., Morris, K. L., Shannon, J. G., Robertson, S. J., Mitzel, D. N., Park, G. S., Boer, E., Wolfinbarger, J. B. and Bloom, M. E. (2005) Inhibition of interferon-stimulated JAK-STAT signaling by a tick-borne flavivirus and identification of NS5 as an interferon antagonist. J. Virol. 79, 12828-12839. https://doi.org/10.1128/JVI.79.20.12828-12839.2005
  3. Chae, D., Manzoor, Z., Kim, S. C., Kim, S., Oh, T. H., Yoo, E. S., Kang, H. K., Hyun, J. W., Lee, N. H., Ko, M. H. and Koh, Y. S. (2013) Apo-9'-fucoxanthinone, isolated from Sargassum muticum, inhibits CpG-induced inflammatory response by attenuating the mitogenactivated protein kinase pathway. Mar. Drugs 11, 3272-3287. https://doi.org/10.3390/md11093272
  4. Choi, H. J., Park, J. H., Lee, B. H., Chee, H. Y., Lee, K. B. and Oh, S. M. (2014) Suppression of NF-kappaB by dieckol extracted from Ecklonia cava negatively regulates LPS induction of inducible nitric oxide synthase gene. Appl Biochem Biotechnol 173, 957-967. https://doi.org/10.1007/s12010-014-0910-6
  5. Decker, T. and Kovarik, P. (2000) Serine phosphorylation of STATs. Oncogene 19, 2628-2637. https://doi.org/10.1038/sj.onc.1203481
  6. Farrar, M. A. and Schreiber, R. D. (1993) The molecular cell biology of interferon-gamma and its receptor. Annu. Rev. Immunol. 11, 571-611. https://doi.org/10.1146/annurev.iy.11.040193.003035
  7. Han, S. K., Song, J. Y., Yun, Y. S. and Yi, S. Y. (2002) Gamma irradiation-reduced IFN-gamma expression, STAT1 signals, and cellmediated immunity. J. Biochem. Mol. Biol. 35, 583-589. https://doi.org/10.5483/BMBRep.2002.35.6.583
  8. Ivashkiv, L. B. and Hu, X. (2004) Signaling by STATs. Arthritis Res. Ther. 6, 159-168. https://doi.org/10.1186/ar1197
  9. Jahnz-Rozyk, K., Targowski, T., Paluchowska, E., Owczarek, W. and Kucharczyk, A. (2005) Serum thymus and activation-regulated chemokine, macrophage-derived chemokine and eotaxin as markers of severity of atopic dermatitis. Allergy 60, 685-688. https://doi.org/10.1111/j.1398-9995.2005.00774.x
  10. Ju, S. M., Song, H. Y., Lee, S. J., Seo, W. Y., Sin, D. H., Goh, A. R., Kang, Y. H., Kang, I. J., Won, M. H., Yi, J. S., Kwon, D. J., Bae, Y. S., Choi, S. Y. and Park, J. (2009) Suppression of thymus- and activation-regulated chemokine (TARC/CCL17) production by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose via blockade of NF-kappaB and STAT1 activation in the HaCaT cells. Biochem. Biophys. Res. Commun. 387, 115-120. https://doi.org/10.1016/j.bbrc.2009.06.137
  11. Jung, H. A., Jin, S. E., Ahn, B. R., Lee, C. M. and Choi, J. S. (2013) Anti-inflammatory activity of edible brown alga Eisenia bicyclis and its constituents fucosterol and phlorotannins in LPS-stimulated RAW264.7 macrophages. Food Chem. Toxicol. 59, 199-206. https://doi.org/10.1016/j.fct.2013.05.061
  12. Kang, M. C., Ahn, G., Yang, X., Kim, K. N., Kang, S. M., Lee, S. H., Ko, S. C., Ko, J. Y., Kim, D., Kim, Y. T., Jee, Y., Park, S. J. and Jeon, Y. J. (2012a) Hepatoprotective effects of dieckol-rich phlorotannins from Ecklonia cava, a brown seaweed, against ethanol induced liver damage in BALB/c mice. Food Chem. Toxicol. 50, 1986-1991. https://doi.org/10.1016/j.fct.2012.03.078
  13. Kang, M. C., Wijesinghe, W. A., Lee, S. H., Kang, S. M., Ko, S. C., Yang, X., Kang, N., Jeon, B. T., Kim, J., Lee, D. H. and Jeon, Y. J. (2013) Dieckol isolated from brown seaweed Ecklonia cava attenuates type capital I, Ukrainiancapital I, Ukrainian diabetes in db/db mouse model. Food Chem. Toxicol. 53, 294-298. https://doi.org/10.1016/j.fct.2012.12.012
  14. Kang, S. M., Heo, S. J., Kim, K. N., Lee, S. H., Yang, H. M., Kim, A. D. and Jeon, Y. J. (2012b) Molecular docking studies of a phlorotannin, dieckol isolated from Ecklonia cava with tyrosinase inhibitory activity. Bioorg. Med. Chem. 20, 311-316. https://doi.org/10.1016/j.bmc.2011.10.078
  15. Kang, G. J., Lee, H. J., Yoon, W. J., Yang, E. J., Park, S. S., Kang, H. K., Park, M. H. and Yoo, E. S. (2008) Prunus yedoensis inhibits the inflammatory chemokines, MDC and TARC, by regulating the STAT1-signaling pathway in IFN-${\gamma}$-stimulated HaCaT human keratinocytes. Biomol. Ther. 16, 394-402. https://doi.org/10.4062/biomolther.2008.16.4.394
  16. Kim, S. K. and Himaya, S. W. (2011) Medicinal effects of phlorotannins from marine brown algae. Adv. Food Nutr. Res. 64, 97-109. https://doi.org/10.1016/B978-0-12-387669-0.00008-9
  17. Kim, K. C., Piao, M. J., Zheng, J. Y., Cheng, W., Cha, J. W., Kumara, M. H. S. R., Han, Xia., Kang, H. K., Lee, N. H. and Hyun, J. W. (2014) Fucodiphlorethol G purified from Ecklonia cava suppresses ultraviolet B radiation-induced oxidative stress and cellular damage. Biomol. Ther. 22, 301-307. https://doi.org/10.4062/biomolther.2014.044
  18. Lee, S. H., Park, M. H., Kang, S. M., Ko, S. C., Kang, M. C., Cho, S., Park, P. J., Jeon, B. T., Kim, S. K., Han, J. S. and Jeon, Y. J. (2012) Dieckol isolated from Ecklonia cava protects against high-glucose induced damage to rat insulinoma cells by reducing oxidative stress and apoptosis. Biosci. Biotechnol. Biochem. 76, 1445-1451. https://doi.org/10.1271/bbb.120096
  19. Madonna, S., Scarponi, C., De Pita, O. and Albanesi, C. (2008) Suppressor of cytokine signaling 1 inhibits IFN-gamma inflammatory signaling in human keratinocytes by sustaining ERK1/2 activation. FASEB J. 22, 3287-3297. https://doi.org/10.1096/fj.08-106831
  20. Maeda, S., Fujiwara, S., Omori, K., Kawano, K., Kurata, K., Masuda, K., Ohno, K. and Tsujimoto, H. (2002) Lesional expression of thymus and activation-regulated chemokine in canine atopic dermatitis. Vet. Immunol. Immunopathol. 88, 79-87. https://doi.org/10.1016/S0165-2427(02)00140-X
  21. Park, J. Y., Kim, J. H., Kwon, J. M., Kwon, H. J., Jeong, H. J., Kim, Y. M., Kim, D., Lee, W. S. and Ryu, Y. B. (2013) Dieckol, a SARS-CoV 3CL(pro) inhibitor, isolated from the edible brown algae Ecklonia cava. Bioorg. Med. Chem. 21, 3730-3737. https://doi.org/10.1016/j.bmc.2013.04.026
  22. Park, S. J. and Jeon, Y. J. (2012) Dieckol from Ecklonia cava suppresses the migration and invasion of HT1080 cells by inhibiting the focal adhesion kinase pathway downstream of Rac1-ROS signaling. Mol. Cells 33, 141-149. https://doi.org/10.1007/s10059-012-2192-6
  23. Pearson, G., Robinson, F., Beers Gibson, T., Xu, B. E., Karandikar, M., Berman, K. and Cobb, M. H. (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr. Rev. 22, 153-183.
  24. Qi, X. F., Kim, D. H., Yoon, Y. S., Li, J. H., Jin, D., Teng, Y. C., Kim, S. K. and Lee, K. J. (2009) Fluvastatin inhibits expression of the chemokine MDC/CCL22 induced by interferon-gamma in HaCaT cells, a human keratinocyte cell line. Br. J. Pharmacol. 157, 1441-1450. https://doi.org/10.1111/j.1476-5381.2009.00311.x
  25. Rauch, I., Muller, M. and Decker, T. (2013) The regulation of inflammation by interferons and their STATs. JAKSTAT 2, e23820.
  26. Saeki, H. and Tamaki, K. (2006) Thymus and activation regulated chemokine (TARC)/CCL17 and skin diseases. J. Dermatol. Sci. 43, 75-84. https://doi.org/10.1016/j.jdermsci.2006.06.002
  27. Semper, C., Leitner, N. R., Lassnig, C., Parrini, M., Mahlakoiv, T., Rammerstorfer, M., Lorenz, K., Rigler, D., Muller, S., Kolbe, T., Vogl, C., Rulicke, T., Staeheli, P., Decker, T., Muller, M. and Strobl, B. (2014) STAT1beta is not dominant negative and is capable of contributing to gamma interferon-dependent innate immunity. Mol. Cell. Biol. 34, 2235-2248. https://doi.org/10.1128/MCB.00295-14
  28. Shimada, Y., Takehara, K. and Sato, S. (2004) Both Th2 and Th1 chemokines (TARC/CCL17, MDC/CCL22, and Mig/CXCL9) are elevated in sera from patients with atopic dermatitis. J. Dermatol. Sci. 34, 201-208. https://doi.org/10.1016/j.jdermsci.2004.01.001
  29. van den Broek, M. F., Muller, U., Huang, S., Zinkernagel, R. M. and Aguet, M. (1995) Immune defence in mice lacking type I and/or type II interferon receptors. Immunol. Rev. 148, 5-18. https://doi.org/10.1111/j.1600-065X.1995.tb00090.x
  30. Wijesinghe, W. A., Ko, S. C. and Jeon, Y. J. (2011) Effect of phlorotannins isolated from Ecklonia cava on angiotensin I-converting enzyme (ACE) inhibitory activity. Nutr. Res. Pract. 5, 93-100. https://doi.org/10.4162/nrp.2011.5.2.93
  31. Yamashita, U. and Kuroda, E. (2002) Regulation of macrophage-derived chemokine (MDC, CCL22) production. Crit. Rev. Immunol. 22, 105-114.
  32. Yayeh, T., Im, E. J., Kwon, T. H., Roh, S. S., Kim, S., Kim, J. H., Hong, S. B., Cho, J. Y., Park, N. H. and Rhee, M. H. (2014) Hemeoxygenase 1 partly mediates the anti-inflammatory effect of dieckol in lipopolysaccharide stimulated murine macrophages. Int. Immunopharmacol. 22, 51-58. https://doi.org/10.1016/j.intimp.2014.06.009
  33. Yoon, W. J., Kim, K. N., Heo, S. J., Han, S. C., Kim, J., Ko, Y. J., Kang, H. K. and Yoo, E. S. (2013) Sargachromanol G inhibits osteoclastogenesis by suppressing the activation NF-kappaB and MAPKs in RANKL-induced RAW 264.7 cells. Biochem. Biophys. Res. Commun. 434, 892-897. https://doi.org/10.1016/j.bbrc.2013.04.046
  34. Yoshie, O., Imai, T. and Nomiyama, H. (2001) Chemokines in immunity. Adv. Immunol. 78, 57-110. https://doi.org/10.1016/S0065-2776(01)78002-9

Cited by

  1. Eckol fromEisenia bicyclisInhibits Inflammation Through the Akt/NF-κB Signaling inPropionibacterium acnes-Induced Human Keratinocyte Hacat Cells vol.41, pp.2, 2017, https://doi.org/10.1111/jfbc.12312
  2. Marine natural products vol.34, pp.3, 2017, https://doi.org/10.1039/C6NP00124F
  3. Recent advances in pharmacological research on Ecklonia species: a review vol.40, pp.9, 2017, https://doi.org/10.1007/s12272-017-0948-4
  4. vol.33, pp.4, 2017, https://doi.org/10.5487/TR.2017.33.4.325
  5. Anti-Neuroinflammatory Property of Phlorotannins from Ecklonia cava on Aβ 25-35 -Induced Damage in PC12 Cells vol.17, pp.1, 2015, https://doi.org/10.3390/md17010007
  6. Anti-Atopic Dermatitis Effect of Seaweed Fulvescens Extract via Inhibiting the STAT1 Pathway vol.2019, pp.None, 2015, https://doi.org/10.1155/2019/3760934
  7. Eckol Inhibits Particulate Matter 2.5-Induced Skin Keratinocyte Damage via MAPK Signaling Pathway vol.17, pp.8, 2019, https://doi.org/10.3390/md17080444
  8. 7,8-dimethoxycoumarin Attenuates the Expression of IL-6, IL-8, and CCL2/MCP-1 in TNF-α-Treated HaCaT Cells by Potentially Targeting the NF-κB and MAPK Pathways vol.6, pp.3, 2015, https://doi.org/10.3390/cosmetics6030041
  9. Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, Antiviral, and Anthelmintic Activities; Affe vol.18, pp.1, 2020, https://doi.org/10.3390/md18010005
  10. Dieckol: an algal polyphenol attenuates urban fine dust-induced inflammation in RAW 264.7 cells via the activation of anti-inflammatory and antioxidant signaling pathways vol.32, pp.4, 2015, https://doi.org/10.1007/s10811-019-01964-w
  11. Dieckol isolated from a brown alga, Eisenia nipponica , suppresses ear swelling from allergic inflammation in mouse vol.45, pp.4, 2015, https://doi.org/10.1111/jfbc.13659
  12. The Effectiveness of Ecklonia Cava Kjellman Extract in Improving Menopausal Syndrome in Osteoporosis and Depression vol.11, pp.12, 2021, https://doi.org/10.3390/app11125315
  13. Dieckol: a brown algal phlorotannin with biological potential vol.142, pp.None, 2015, https://doi.org/10.1016/j.biopha.2021.111988
  14. The Anti-Allergic and Anti-Inflammatory Effects of Phlorotannins from the Edible Brown Algae, Ecklonia sp. and Eisenia sp vol.16, pp.12, 2015, https://doi.org/10.1177/1934578x211060924