Abstract
Activated nuclear factor-kappa B (NF-κB), a well-known transcription factor, leads to the development, differentiation, and proliferation of T and B lymphocytes and the secretion of cytokines by the classical pathway. We have examined here whether an enzymatic extract (ECK) from the brown seaweed, Alariaceae Laminariales Ecklonia cava may contribute to activating lymphocytes through the NF-κB pathway for participation in immune responses. In our study, ECK dose-dependently enhanced the proliferation of lymphocytes. ECK significantly increased the phosphorylation of inhibitors of κB at 0.25 and 0.5 h of exposure, followed by its gradual decrease. In addition, NF-κB p65 was gradually activated, and its binding to nuclear deoxyribonucleic acid was observed from 0.25 h after stimulation (up to 0.5 h). Further experiments showed that the application of N-p-tosyl-l-phenylalanine chloromethyl ketone, an NF-κB inhibitor, significantly blocked ECK-induced lymphocyte's proliferation and the interleukin (IL)-2 productions. Accordingly, our results suggest that ECK increases the production of IL-2 through the activation of NF-κB then induces the proliferation of lymphocytes with the coordinated stimulation of IL-2.





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Ahn GN, Kim KN, Cha SH, Song CB, Lee J, Heo MS, Yeo IK, Lee NH, Jee Y, Kim JS, Heu MS, Jeon YJ (2007) Antioxidant activities of phlorotannins purified from Ecklonia cava on free radical scavenging using ESR and H2O2-mediated DNA damage. Eur Food Res Technol 226:71–79
Ahn G, Hwang IS, Park EJ, Kim JH, Jeon YJ, Jee Y (2008) Immunomodulatory effects of an enzymatic extract from Ecklonia cava on murine splenocytes. Mar Biotechnol 10:278–289
Armitage RJ, Alderson MR (1995) B-cell stimulation. Curr Opin Immunol 7(2):243–247
Ashkenazi A, Dixit VM (1999) Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11:255–260
Athukorala Y, Jung WK, Vasanthan T, Jeon YJ (2006) An anticoagulative polysaccharide from an enzymatic hydrolysate of Ecklonia cava. Carbohyd Polym 66:184–191
Barkett M, Gilmore TD (1999) Control of apoptosis by Rel/NF-kappaB transcription factors. Oncogene 18:6910–6924
Beg AA, Finco TS, Nantermet PV, Baldwin AS Jr (1993) Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of I kappa B alpha: a mechanism for NF-kappa B activation. Mol Cell Biol 13:3301–3310
Breithaupt TB, Vazquez A, Baez I, Eylar EH (1996) The suppression of T cell function and NFκB expression by serine protease inhibitors is blocked by N-acetylcysteine. Cell Immunol 173:124–130
Chan KF, Siegel MR, Lenardo JM (2000) Signaling by the TNF receptor superfamily and T cell homeostasis. Immunity 13:419–422
Cordle SR, Donald R, Read MA, Hawiger J (1993) Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells. J Biol Chem 268:11803–11810
Gerondakis S, Grumont R, Rourke I, Grossmann M (1998) The regulation and roles of Rel/NF-κB transcription factors during lymphocyte activation. Curr Opin Immunol 10:353–359
Golks A, Tran TT, Goetschy JF, Guerini D (2007) Requirement for O-linked N-acetylglucosaminyltransferase in lymphocytes activation. EMBO J 26:4368–4379
Granucci F, Zanoni I, Feau S, Ricciardi-Castagnoli P (2003) Dendritic cell regulation of immune responses: a new role for interleukin 2 at the intersection of innate and adaptive immunity. EMBO J 22(11):2546–2551
Guiry MD, Bulunden G (1991) Seaweed resource in Europe: uses and potential. John Wiley & Sons Ltd, Chichester West Sussex, England
Henkel T, Machleidt T, Akalay I, Kronke M, Ben-Neriah Y, Baeuerle P (1993) Rapid proteolysis of I kappa B-alpha is necessary for activation of transcription factor NF-kappa B. Nature 365:182
Heo SJ, Jeon YJ, Lee J, Kim HT, Lee KW (2003) Antioxidant effect of enzymatic hydrolyzate from a kelp, Ecklonia cava. Algae 18:341–347
Hwang HJ, Kwon MJ, Kim IH, Nam TJ (2008) The effect of polysaccharide extracted from the marine alga Capsosiphon fulvescens on ethanol administration. Food chem Toxicol 46:2653–2657
Ishimaru N, Kishimoto H, Hayashi Y, Sprent J (2006) Regulation of naive T cell function by the NF-kappaB2 pathway. Nat Immunol 7:763–772
Kang KA, Lee KH, Chae SW, Koh YS, Yoo BS, Kim JH, Ham YM, Baik JS, Lee NH, Hyun JW (2005a) Triphlorethol-A from Ecklonia cava protects V79-4 lung fibroblasts against hydrogen peroxide induced cell damage. Free Radic Res 39:883–892
Kang KA, Lee KH, Chae SW, Zhang R, Jung MS, Lee YG, Kim SY, Kim HS (2005b) Eckol isolated from Ecklonia cava attenuates oxidative stress induced cell damage in lung fibroblast cells. FEBS letters 579:6295–6304
Kim KN, Heo SJ, Song CB, Lee JH, Heo MS, Yeo IK, Kang KY, Hyun JW, Jeon YJ (2006a) Protective effect of Ecklonia cava enzymatic extracts on hydrogen peroxide-induced cell damage. Process Biochem 41:2393–2240
Kim MM, Ta QV, Mendis E, Rajapakse N, Jung WK, Gyun HG, Jeon YJ, Kim SK (2006b) Phlorotannins in Ecklonia cava extract inhibit matrix metalloproteinase activity. Life Sciences 79:1436–1443
Le Bail O, Schmidt-Ullrich R, Israël A (1993) Promoter analysis of the gene encoding the I kappa B-alpha/MAD3 inhibitor of NF-kappa B: positive regulation by members of the rel/NF-kappa B family. EMBO J 12:5043–5049
Mora AL, Corn RA, Stanic AK, Goenka S, Aronica M, Stanley S, Ballard DW, Joyce S, Boothby M (2003) Antiapoptotic function of NF-kappaB in T lymphocytes is influenced by their differentiation status: roles of Fas, c-FLIP, and Bcl-xL. Cell Death Differ 10:1032–1044
Pimentel-Muiños FX, Mazana J, Fresno M (1994) Regulation of interleukin-2α chain expression and nuclear factor κB activation by protein kinase C in T lymphocytes. Autocrine role of tumor necrosis factor α. J Biol Chem 269:24424–24429
Prasad AS, Bao B, Beck FW, Sarkar FH (2002) Zinc enhances the expression of interleukin-2 and interleukin-2 receptors in HUT-78 cells by way of NF-κB activation. J Lab Clin Med 140:272–289
Saito H, Yamagata T, Suzuki S (1968) Enzymatic methods for the determination of small quantities of isomeric chondroitin sulfates. J Bio Chem 243:1536–1542
Thompson JE, Phillips RJ, Erdjument-Bromage H, Tempst P, Ghosh S (1995) I kappa B-beta regulates the persistent response in a biphasic activation of NF-kappa B. Cell 80:573–582
Trebilcock GU, Ponnappan U (1996) Induction and regulation of NFkappaB during aging: role of protein kinases. Clin Immunol Immunopathol 79:87–91
Varga G, Dreikhausen U, Kracht M, Appel A, Resch K, Szamel M (1999) Molecular mechanisms of T lymphocyte activation: convergence of T cell antigen receptor and IL-1 receptor-induced signaling at the level of IL-2 gene transcription. Int Immunol 11:1851–1862
Yamamoto Y, Gaynor RB (2001) Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. J Clin Invest 107:135–142
Zabel U, Baeuerle PA (1990) Purified human I kappa B can rapidly dissociate the complex of the NF-kappa B transcription factor with its cognate DNA. Cell 61:255–265
Acknowledgment
This research was performed under the program of Basic Atomic Energy Research Institute (BAERI) which is funded by the Ministry of Science & Technology (MOST) of Korea. The authors wish to thank P. Minick and Tae Hoon Chung for editorial assistance.
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You-Jin Jeon and Youngheun Jee contributed equally to this study.
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Ahn, G., Park, E., Lee, WW. et al. Enzymatic Extract from Ecklonia cava Induces the Activation of Lymphocytes by IL-2 Production Through the Classical NF-κB Pathway. Mar Biotechnol 13, 66–73 (2011). https://doi.org/10.1007/s10126-010-9270-6
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DOI: https://doi.org/10.1007/s10126-010-9270-6


