DOI QR코드

DOI QR Code

Prunus Yedoensis Inhibits the Inflammatory Chemokines, MDC and TARC, by Regulating the STAT1-Signaling Pathway in IFN-γ-stimulated HaCaT Human Keratinocytes

  • Kang, Gyeoung-Jin (Department of pharmacology, School of Medicine, Cheju National University) ;
  • Lee, Hye-Ja (Department of pharmacology, School of Medicine, Cheju National University) ;
  • Yoon, Weon-Jong (Department of pharmacology, School of Medicine, Cheju National University) ;
  • Yang, Eun-Jin (Department of pharmacology, School of Medicine, Cheju National University) ;
  • Park, Sun-Son (Department of pharmacology, School of Medicine, Cheju National University) ;
  • Kang, Hee-Kyoung (Department of pharmacology, School of Medicine, Cheju National University) ;
  • Park, Myung-Hwan (GyeongGi Bio-Center) ;
  • Yoo, Eun-Sook (Department of pharmacology, School of Medicine, Cheju National University)
  • Published : 2008.12.31

Abstract

Atopic dermatitis (AD) is an inflammatory skin disease commonly characterized by infiltration of inflammatory cells into skin lesions. Keratinocytes produce many chemokines that are involved in the pathogenesis of skin disorders. In particular, macrophage-derived chemokine (MDC/CCL22) and thymus and activationregulated chemokine (TARC/CCL17) are Th2-type cytokines. Serum MDC and TARC levels are increased in AD patients. In this study, we investigated the anti-inflammatory effect and mechanism of action of the active fraction from Prunus yedoensis bark. We evaluated their inhibitory effects on the AD-like inflammatory markers (MDC and TARC) and JAK-STAT pathway (STAT1) in HaCaT keratinocytes. The EtOAc fraction of the crude extract (80% EtOH) and the E5 sub-fraction potently inhibited the induction of MDC and TARC mRNA and protein at 50 ${\mu}g$/mL in HaCaT cells. In addition, the E5 sub-fraction inhibited the phosphorylation of STAT1 protein associated with IFN-$\gamma$ signaling transduction in a dose-dependent manner. Thus, P. yedoensis may have antiatopic activity by suppressing the inflammatory chemokines (MDC and TARC).

Keywords

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 JAKSTAT signaling by a tick-borne flavivirus and identification of NS5 as an interferon antagonist. J. Virol. 76,12828-12839 https://doi.org/10.1128/JVI.79.20.12828-12839.2005
  3. Bito, T., Roy, S., Sen, C. K., Shirakawa, T., Gotoh, A., Ueda, M., Ichihashi, M. and Packer, L. (2002). Flavonoids differentially regulate IFN gamma-induced ICAM-1 expression in human keratinocytes: molecular mechanisms of action. FEBS Lett. 520, 145-52 https://doi.org/10.1016/S0014-5793(02)02810-7
  4. Bonncchi, R., Sozzani, S., Stine, J. T., Luini, W., D'Amico, G., Allavena, P., Chantry, D. and Mautovani. A. (1998). Divergent effects of Interleukin-4 and Interferon-${\gamma}$ on Macrophage-Derived Chemokine production : An amplification circuit of polarized T helper 2 responses. Blood 92, 2668-2671
  5. Bordignon, V, Sinagra J. L., Trento E., Pietravalle M., Capitanio, B. and Fei, P. C. (2005). Antigen specific cytokine response in pediatric patients with atopic dermatitis. Pediatr Allergy Immunol. 16,113-120 https://doi.org/10.1111/j.1399-3038.2005.00223.x
  6. Chiang, Y. M, Lo, C. P., Chen, Y. P., Wang, S. Y., Yang, N. S., Kuo, Y. H., and Shyur, L. F. (2005). Ethyl caffeate suppresses NF-kappaB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin. Br .J. Pharmacol. 146, 352-63 https://doi.org/10.1038/sj.bjp.0706343
  7. Esche, C., de Benedetto, A. and Beck, L. A. (2004). Keratinocytes in atopic dermatitis: Inflammatory signals. Cur. Allergy Asthma Rep. 4, 276-284 https://doi.org/10.1007/s11882-004-0071-8
  8. Fujisawa, T., Fujisawa, R., Kato, Y., Nakayama, T., Morita, A., Katsumata, H., Nishimori, H., Iguchi, K., kamiya, H., Gray, P. W., Chantry, D., Suzuki, R. and Yoshie, O. (2002). Presence of high contents of thymus and activation-regulated chemokine in platelets and elevated plasma levels of thymus and activation-regulated chemokine and macrophage-derived chemokine in patients with atopic dermatitis. J. Allergy Clin. Immunol. 110, 139-146 https://doi.org/10.1067/mai.2002.126079
  9. Godiska, R., Chantry, D., Raport, C. J., Sozzanl, S., Allavena, P., Leviten, D., Mantovani, A. and Gray, P. W. (1997). Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes, monocyte-derived dendritic cells, and natural killer cells. J. Exp. Med. 185, 1595-1604 https://doi.org/10.1084/jem.185.9.1595
  10. Grewe, M., Gyufko, K., Schopf, E. and Krutmann, J. (1994). Expression of interferon-gamma in atopic eczema. Lancet 343, 25-26 https://doi.org/10.1016/S0140-6736(94)90879-6
  11. Hamalainen, M., Nieminen, R., Vuorela, P., Heinonen, M., and Moilanen, E. (2007). Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007, 45673
  12. Han, B. H. and Han, Y. N. (1978). Immunosuppressant activity of cheery bark extract. Kor. J. Pharmacog. 9, 173-175
  13. 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
  14. Hijnen, D., De Bruin-Weller, M., Oosting, B., Lebre C., De Jong, E., Bruijnzeel-Koomen, C. and Knol, E. (2004). Serum thymus and activation-regulated chemokine (TARC) and cutaneous T cell-attracting chemokine (CTACK) levels in allergic diseases: TARC and CTACK are disease-specific markers for atopic dermatitis. J. Allergy Clin. Immunol. 113, 334-40 https://doi.org/10.1016/j.jaci.2003.12.007
  15. Horikawa, T., Nakayama, T., Hikita, I., Yamada, H., Fujisawa, R., Bito, T., Harada, S., Fukunaga, A., Chantry, D., Gray, P. W., Morita, A., Suzuki, R., Tezuka, T., Ichihashi, M. and Yoshie, O. (2002). IFN-${\gamma}$-inducible expression of thymus and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in epidermal keratinocytes and their roles in atopic dermatitis. Int. Immunol. 7, 767-773
  16. Ivashkiv, L. B. and Hu, X. (2004). Signaling by STATs. Arthritis Res. Ther. 6, 159-168 https://doi.org/10.1186/ar1197
  17. Jakubzick, C., Wen, H., Matsukawa, A., Keller, M., Kunkel, S. L. and Hogaboam, C. M. (2004). Role of CCL4 ligands, CCL17 and CCL22, during schistosoma mansoni egg-induced pulmonary granuloma formation in mice. Am. J. Pathol. 165, 1211-1221 https://doi.org/10.1016/S0002-9440(10)63381-0
  18. Kakinuma, T., Nakamura, K., Wakugawa, M., Mitsui, H., Tada, Y., Saeki, H., Torii, H., Komine, M., Asahina, A. and Tamaki, K. (2002). Serum macrophage-derived chemokine (MDC) levels are closely related with the disease activity of atopic dermatitis. Clin. Exp. Immunol. 127, 270-273 https://doi.org/10.1046/j.1365-2249.2002.01727.x
  19. Kanda, N. and Watanabe, S. (2007). Prolactin enhances interferon-g-induced production of CXC ligand 9 (CXCL9), CXCL10, and CXCL11 in human keratinocytes. Endocrinol. 148, 2317-2325 https://doi.org/10.1210/en.2006-1639
  20. Komine, M. and Kakinuma, T., Kagami, S., Hanakawa, Y., Hashimoto, K., Tamaki, K. (2005). Mechanism of thymus- and activation-regulated chemokine(TARC)/CCL17 production and its modulation by roxithromycin. J. Invest. Dermatol. 125, 491-498 https://doi.org/10.1111/j.0022-202X.2005.23840.x
  21. Luster, A. D. (2001). Antichemokine immunotherapy for allergic diseases. Allergy Clin. Immunol. 1, 561-567
  22. Nakazato, J., Kishida, M., Kuroiwa, R., Fujiwara, J., Shimoda, M., and Shinomiya, N. (2008). Serum levels of Th2 chemokines, CCL17, CCl22, and CCl27, were the important markers of severity in infantile atopic dermatitis. Pediatr. Allergy Immunol. 1, 10 https://doi.org/10.1111/j.1399-3038.2007.00692.x
  23. Noshita, T., Sakaguchi, A., and Funayama, S. (2006). Isolation of ethyl caffeate from the petals of Prunus yedoensis J. Nat. Med. 60, 266-267 https://doi.org/10.1007/s11418-006-0033-7
  24. Park, E. S., Shin, M. K. and Song, H. J. (1998). A study on the antiallergic effect of cortex betula platyphyllae or cortex pruni serrulatae extract. Kor. J. Herbology. 13, 57-69
  25. Portengen, L., Sigsgaard, T., Omland, O, Hjort, C., Heederik, D., and Doekes, G. (2002). Low prevalence of atopy in young Danish farmers and farming students born and raised on a farm. Clin. Exp. Allergy. 32, 247-253 https://doi.org/10.1046/j.1365-2222.2002.01310.x
  26. Rozyk, K. J., Targowski, T., Paluchowska, E., Owczarek, W. and Kucharczyk, A. (2005). Serum thymus and activation-regulated chemokine, Macrophage-derived chemokine and eotaxin as marker of severity of atopic dermatitis. Allergy 60, 685-688 https://doi.org/10.1111/j.1398-9995.2005.00774.x
  27. Saeki, H. and Tamaki, K. (2006). Thymus and activation regulated chemokine(TARC)/CCL17 and skin diseases. J. Dermatol. Clin. Exp. Allergy 43, 75-84 https://doi.org/10.1016/S1043-4666(03)00221-7
  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. Clin. Exp. Allergy 24, 201-208 https://doi.org/10.1016/j.jdermsci.2004.01.001
  29. Strobl, B., Arulampalam, V., Is'harc, H., Newman, S. J., Schlaak, J. F., Watling, D., Costa-Pereira, A. P., Schaper, F., Behrman, I., Sheehan, K. C. F., Schreiber, R. D., Horn, F., Heinrich, P.C. and Kerr, I. M. (2001). A completely foreign receptor can mediate an interferon-${\gamma}$-like response. EMBO J. 20, 5431-5442 https://doi.org/10.1093/emboj/20.19.5431.
  30. Vestergaard, C., Yoneyama, H., Murai, M., Nakamura, K., Tamaki, K., Terashima, Y., Imai, T., Yoshie, O., Irimura, T., Mizutani, H. and Matsushima, K. (1999). Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis-like lesions. J. Clin. Clin. Exp. Allergy 104, 1097-1105 https://doi.org/10.1172/JCI7613
  31. Wormald, S., Hilton, D. J., Smyth, G. K. and Speed, T. P. (2006). Proximal genomic localization of STAT1 binding and regulated transcriptional activity. BMC Genomics. 7, 254 https://doi.org/10.1186/1471-2164-7-254
  32. Xiao, T., Kagami, S., Saeki, H., Sugaya, M., Kakinuma, T., Fujita, H., Yano, S., Mitsui, H., Torii, H., Komine, M., Asahina, A., Nakamura, K. and Tamaki, K. (2003). Both IL-4 and IL-13 inhibit the TNF-α and IFN-γ enhanced MDC production in a human keratinocyte cell line, HaCaT cells. J. Dermatol. Sci. 31, 111-117 https://doi.org/10.1016/S0923-1811(02)00149-4
  33. Yu, B., Koga, T., Urabe, K., Moroi, Y., Maeda, S., Yanagihara, Y. and Furue, M. (2002). Differential regulation of thymus- and activation-regulated chemokine induced by IL-4, IL-13, TNFalpha and IFN-gamma in human keratinocyte and fibroblast. J. Dermatol. Sci. 30, 29-36 https://doi.org/10.1016/S0923-1811(02)00046-4

Cited by

  1. Apamin inhibits TNF-α- and IFN-γ-induced inflammatory cytokines and chemokines via suppressions of NF-κB signaling pathway and STAT in human keratinocytes 2017, https://doi.org/10.1016/j.pharep.2017.04.006
  2. Prunus yedoensisBark Inhibits Lipopolysaccharide-Induced Inflammatory Cytokine Synthesis by IκBα Degradation and MAPK Activation in Macrophages vol.17, pp.4, 2014, https://doi.org/10.1089/jmf.2013.2825
  3. Dieckol, a Component of Ecklonia cava, Suppresses the Production of MDC/CCL22 via Down-Regulating STAT1 Pathway in Interferon-γ Stimulated HaCaT Human Keratinocytes vol.23, pp.3, 2015, https://doi.org/10.4062/biomolther.2014.141
  4. Effect of Prunus yedoensis Matsumura extract on the gene expression in HaCaT cells vol.14, pp.3, 2018, https://doi.org/10.1007/s13273-018-0037-x
  5. Cinnamomum camphora Leaves Alleviate Allergic Skin Inflammatory Responses In Vitro and In Vivo vol.35, pp.3, 2008, https://doi.org/10.5487/tr.2019.35.3.279