Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Protective Effect of Dried Mackerel Extract on Lipopolysaccharide-induced Inflammation

Lipopolysaccharide (LPS)에 의해 유도된 염증에 대한 건조 고등어 추출물의 항염증 효과

  • Kim, Kwang-Hyuk (Department Microbiology, Kosin University College of Medicine) ;
  • Choi, Myoung Won (Department Microbiology, Kosin University College of Medicine) ;
  • Choi, Hyang Mi (Division of Marine Environment & Bioscience, Korea Maritime and Ocean University) ;
  • Lim, Sun-Young (Division of Marine Environment & Bioscience, Korea Maritime and Ocean University)
  • 김광혁 (고신대학교 의과대학 미생물학 교실) ;
  • 최명원 (고신대학교 의과대학 미생물학 교실) ;
  • 최향미 (한국해양대학교 해양환경생명과학부) ;
  • 임선영 (한국해양대학교 해양환경생명과학부)
  • Received : 2013.08.02
  • Accepted : 2013.09.09
  • Published : 2013.09.30
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Abstract

The effect of dried mackerel extract on the production of nitric oxide (NO) and cytokines, including interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was investigated. All extracts and fractions from dried mackerel significantly reduced NO production induced by lipopolysaccharide (LPS). Among the extracts, acetone+methylene chloride (A+M), n-hexane, and 85% aqueous methanol (MeOH) showed the strongest inhibitory effects. The 85% aqueous MeOH fraction at a concentration of $10{\mu}g$ significantly decreased LPS-induced IL-6 and TNF-${\alpha}$ production after 6 hr of incubation. In the case of LPS-induced IFN-${\gamma}$ production, the 85% aqueous MeOH fraction decreased the production of IFN-${\gamma}$ afer 6, 24, and 72 hr of incubation in a dose-dependent manner. The results show that an 85% aqueous MeOH fraction inhibits the production of NO and proinflammatory cytokines (IL-6, TNF-${\alpha}$, IFN-${\gamma}$), suggesting that this fraction acts as a potent immunomodulator.

본 연구에서는 건조 고등어 추출물 및 분획물들에 의한 nitric oxide 생성에 미치는 영향을 살펴보았고 건조 고등어 85% aq. MeOH 분획물을 중심으로 면역과정의 생물학적 작용과 대사적 변화를 유도하는 IL-6, IFN-${\gamma}$ 및 TNF-${\alpha}$ 같은 pro-inflammatory 사이토카인의 생성을 측정하여 건조 고등어 추출물에 의한 항염증 효과에 대하여 검토하였다. 건조 고등어 추출물과 각 분획물은 control보다 낮은 nitric oxide 생성량을 나타내었으며, 특히 85% aq. MeOH 및 n-hexane 분획물에 의한 저해효과가 높았다. 건조 고등어 분획물은 Con-A 보다는 LPS에 의해 자극된 IL-6, TNF-${\alpha}$ 및 IFN-${\gamma}$의 생성을 감소시키는데 더 효과적이었다. IL-6 및 TNF-${\alpha}$의 생성은 배양시간 6시간 후 건조 고등어 85% aq. MeOH 분획물의 모든 첨가농도(1, 3 및 $10{\mu}g$)에서 감소되었다(p<0.05). IFN-${\gamma}$의 경우, 건조 고등어 85% aq. MeOH 분획물을 LPS와 함께 처리했을 때 특히 72시간 배양 시 IFN-${\gamma}$의 생성량이 농도 의존적으로 감소하였고 Con-A에 의해 자극된 IFN-${\gamma}$의 생성량은 6 및 24시간 배양 후 유의적으로 감소하였다(p<0.05). 이상의 결과로부터 건조 고등어 85% aq. MeOH 분획물은 nitric oxide 생성과 pro-inflammatory 사이토카인(IL-6, TNF-${\alpha}$, and IFN-${\gamma}$)을 감소시켜 염증반응을 예방할 것으로 기대된다.

Keywords

References

  1. Axtelle, T. and Pribble, J. 2001. IC14, a CD14 specific monoclonal antibody, is a potential treatment for patients with severe sepsis. J Endotoxin Res 7, 310-314. https://doi.org/10.1179/096805101101532783
  2. Bouwens, M., van de Rest, O., Dellsscharft, N., Bromhaar, M. G., de Groot, L. C., Geleijinse, J. M., Muller, M. and Afman, L. A. 2009. Fish-oil supplementation induces antiinflammatory gene expression profiles in human blood mononuclear cells. Am J Clin Nutr 90, 415-424. https://doi.org/10.3945/ajcn.2009.27680
  3. Brown, K. L., Cosseau, C., Gardy, J. L. and Hancock, R. E. 2007. Complexities of targeting innate immunity to treat infection. Trends Immunol 28, 260-266. https://doi.org/10.1016/j.it.2007.04.005
  4. Calder, P. C. 2008. The relationship between the fatty acid composition of immune cells and their function. Prostagglandins Leukot Essent Fatty Acids 79, 101-108. https://doi.org/10.1016/j.plefa.2008.09.016
  5. Caughey, G. E., Mantzioris, E., Gibson, R. A., Cleland, L. G. and James, M. J. 1996. The effect on human tumor necrosis factor and a interleukin 1$\beta$ production of diets enriched in n-3 fatty acid from vegetable oil or fish oil. Am J Clin Nutr 63, 116-122.
  6. Delgado, A. V., McManus, A. T. and Chambers, J. P. 2003. Production of tumor necrosis factor-alpha, interleukin 1-beta, interleukin-2, and interleukin-6 by rat leukocyte subpopulation after exposure to substance P. Neuropeptides 37, 355-361. https://doi.org/10.1016/j.npep.2003.09.005
  7. De Smedt-Peyrusse, V., Sargueil, F., Moranis, A., Harizi, H., Mongrand, S. and Laye, S. 2008. Docosahexaenoic acid prevents lipopolysaccharide-induced cytokine production in microglial cells by inhibiting lipopolysaccharide receptor presentation but not its membrane subdomain localization. J Neurochem 105, 296-307. https://doi.org/10.1111/j.1471-4159.2007.05129.x
  8. Feldmann, M., Brennan, F. M. and Maini, R. N. 1996. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14, 397-440. https://doi.org/10.1146/annurev.immunol.14.1.397
  9. Green, L. C., Wagner, D. A., Logowski, G. J., Skipper, P. L., Wishnok, J. S. and Tannenbaum, S. R. 1982. Analysis of nitrate, nitrite and [15N] nitrate in biological fluids. Anal Biochem 126, 131-138. https://doi.org/10.1016/0003-2697(82)90118-X
  10. Hwang, S. A., Dasgupta, A. and Actor, J. K. 2004. Cytokine production by non-adherent mouse splenocyte cultures to Echinacea extracts. Clin Chim Acta 343, 161-166. https://doi.org/10.1016/j.cccn.2004.01.011
  11. Hwang, W. I., Baik, N. G., Hwang, Y. K. and Lee, S. D. 1992. Antitumor and immunological effects of tuna extracts. J Korean Soc Food Nutr 21, 353-366.
  12. Jang, J. R., Choi, H. J., Kim, K. K. and Lim, S. Y. 2008. Effect of extracts from dried mackerel on antioxidant activity and inhibition of growth of human cancer cell lines. J Life Sci 18, 680-685. https://doi.org/10.5352/JLS.2008.18.5.680
  13. Kaltschmidt, B., Sparna, T. and Kaltschnidt, D. 1999. Activation of NF-kappa B by reactive oxygen intermediates in the nervous system. Antioxid Redox Signal 1, 129-144. https://doi.org/10.1089/ars.1999.1.2-129
  14. Khair-El-Din, T., Sicher, S. C., Vazquez, M. A., Chung, G. W., Stallworth, K. A., Kitamura, K., Miller, R. T. and Lu, C. Y. 1996. Transcription of the murine iNOS gene is inhibited by docosahexaenoic acid, a major constituent of fetal and neonatal sera as well as fish oils. J Exp Med 183, 1241-1246. https://doi.org/10.1084/jem.183.3.1241
  15. Kim, J., Lee, C. M., Jeong, H. J., Kim, D. W. and Lee, K. Y. 2012. Elevated anti-inflammatory effects of eicosapentaenoic acid based self-aggregated glycol chitosan nanoparticles. J Nanosci Nanotechnol 12, 2672-2678. https://doi.org/10.1166/jnn.2012.5685
  16. Kim, K. H., Choi, M. W., Choi, H. M. and Lim, S. Y. 2013. Effect of tuna extracts on production of nitric oxide and inflammatory cytokines. J Korean Food Sci 45, 385-390. https://doi.org/10.9721/KJFST.2013.45.3.385
  17. Kim, K. H., Kim, S. H. and Park, K. Y. 2001. Effects of kimchi extracts on production of nitric oxide by activated macrophages, transforming growth factor-beta 1 of tumor cells and interleukin-6 in splenocytes. J Food Sci 6, 126-132.
  18. Lazarov, S., Balutsov, M. and Ianev, E. 2000. The role of bacterial endotoxins, receptors and cytokines in the pathogenesis of septic (endotoxin) shock. Vutr Boles 32, 33-40.
  19. Medina, I., Auboug, S. P. and Martin, R. P. 1995. Composition of phospholipids of white muscle of six tuna species. Lipids 30, 1127-1135. https://doi.org/10.1007/BF02536613
  20. Miyake, K. 2004. Innate recognition of lipopolysaccharide by Toll-like receptor 4-MD-2. Trends Microbiol 12, 186-192. https://doi.org/10.1016/j.tim.2004.02.009
  21. Murase, T. and Saito, H. 1996. The docosahexaenoic acid content in the lipid of albacore Thunnusalalunga caught in the two separate localities. Fish Sci 62, 634-638.
  22. Palacios, R. 1982. Concanavalin A triggers T lymphocytes by directly interactingwith their receptors for activation. J Immunol 361, 98-106.
  23. Posadas, I., Terencio, M. C., Guilln, I., Ferrndiz, M. L., Coloma, J., Pay, M. and Alcaraz, M. J. 2000. Co-regulation between cyclo-oxygenase-2 and inducible nitric oxide synthase expression in the time course of murine inflammation. Naunyn-Schmiedebergs Arch Pharmacol 361, 98-106. https://doi.org/10.1007/s002109900150
  24. Ruxton, C. H., Reed, S. C., Simpson, M. J. A. and Millington, K. J. 2004. The health benefits of omega- polyunsaturated fatty acids. J Hum Nutr Diet 17, 449-459. https://doi.org/10.1111/j.1365-277X.2004.00552.x
  25. Scott, M. G. and Hancock, R. E. 2000. Cationic antimicrobial peptides and their multifunctional role in the immune system. Crit Rev Immunol 20, 407-431.
  26. Stokes, K. Y., Cooper D., Tailor, A. and Granger, D. N. 2002. Hypercholesterolemia promotes inflammation and microvascular dysfunction: role of niric oxide and superoxide. Free Radical Biol Med 33, 1026-1036. https://doi.org/10.1016/S0891-5849(02)01015-8
  27. Tizard, I. R. 1986. Immunology, pp. 423-441, 2nd eds., Saunders College Publishing: An introduction inflammation, NY, USA.
  28. Weldon, S. M., Mullen, A. C., Loscher, C. E., Hurley, L. A. and Roche, H. M. 2007. Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaemoic acid. J Nutr Biochem 18, 250-258. https://doi.org/10.1016/j.jnutbio.2006.04.003
  29. Wu, D., Meydani, S. N., Meydani, M., Hayek, M. G., Huth, P. and Nicolosi, R. J. 1996. Immunologic effects of marineand plant-derived n-3 polyunsaturated fatty acids in nonhuman primates. Am J Clin Nutr 63, 273-280.

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