한국해양바이오학회지 (Journal of Marine Bioscience and Biotechnology)

한국해양바이오학회 (The Korean Society for Marine Biotechnology)
권호 표지
DOI QR코드

DOI QR Code

대식세포에서 괭생이모자반 추출물의 MAPKs 기전 통한 면역활성 증가 효과

Immune enhancing activity of Sargassum horneri extracts via MAPK pathway in macrophages

  • 김동섭 (한국프라임제약(주)) ;
  • 김민지 (한국프라임제약(주)) ;
  • 성낙윤 (한국프라임제약(주)) ;
  • 한인준 (한국프라임제약(주)) ;
  • 김건 (한국프라임제약(주)) ;
  • 김춘성 (조선대학교 치과대학 구강생화학) ;
  • 유영춘 (건양대학교 의과대학 미생물학교실) ;
  • 정윤우 (한국프라임제약(주))
  • 투고 : 2023.02.23
  • 심사 : 2023.05.22
  • 발행 : 2023.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Sargassum horneri (SH), a brown macroalgae, has medicinal properties. The present study investigated the immune-enhancing effects of SH extract on peritoneal macrophages (PM). The SH significantly increased the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in PM. It was confirmed that SH significantly increased NO expression through the increase of iNOS protein expression, which is the up-regulation pathway. Additionally, it was determined if SH activates the mitogen-activated protein kinase (MAPK) pathway, an upper regulatory mechanism that influences TNF-α, IL-6, and NO expression. Consequently, SH significantly increased the phosphorylation of p38, extracellular signal-regulated kinases (ERK), and c-Jun N-terminal kinase (JNK), all of which are MAPK pathway proteins. Moreover, the immune-enhancing effects of SH on another macrophage cell line, bone marrow-derived macrophages were investigated. It was observed that SH significantly enhanced TNF-α, IL-6, and NO production. Overall, this study demonstrates the immune-enhancing effects of SH on macrophages via activated MAPK pathway. Therefore, it suggests that SH has the potential to improve immunological activity in various macrophage cell lines and can be useful as an immune-enhancing treatment.

키워드

과제정보

이 논문은 2021년도 해양수산부 재원으로 해양수산과학기술진흥원의 지원을 받아 수행된 연구임. (20210656, 빅데이터 기반 바이오헬스케어 유효성 소재 실증 지원)

참고문헌

  1. Xiao, H. Zhao, J. Fang, C. Cao, Q. Xing, M. Li, X. Hou, J. Ji, A. and Song, S. Advances in Studies on the Pharmacological Activities of Fucoxanthin, Mar Drugs. 2020 Dec 11; 18(12):634.
  2. Wang Y, Xing M, Cao Q, Ji A, Liang H, and Song S. Biological Activities of Fucoidan and the Factors Mediating Its Therapeutic Effects: A Review of Recent Studies. Mar Dru., 2019 Mar 20; 17(3):183.
  3. Sarithakumari., C. H. Renju. G L. and Muraleedhara Kurup, G. Anti-inflammatory and antioxidant potential of alginic acid isolated from the marine algae, Sargassum wightii on adjuvant-induced arthritic rats. Inflammopharmacology. 2013 Jun; 21(3):261-8. https://doi.org/10.1007/s10787-012-0159-z
  4. Matsumura, Y. Nutrition trends in Japan. APJCN. 2001; 49(4):484-485
  5. Zhuang, M. Liu, J, Ding, X. 2, He, J. Zhao, S. Wu, L. Gao, S. Zhao, C. Liu, D. Zhang, J. and He, P. Sargassum blooms in the East China Sea and Yellow Sea: Formation and management. Mar Pollut Bull. 2021 Jan; 162:111845.
  6. Byeon, S. Cheon, K. S. Kim, S. Yun, S. H. Oh, H. J. Park, S. Kim, T. H. Kim, J. and Lee, H. Comparative Analysis of Sequence Polymorphism in Complete Organelle Genomes of the 'Golden Tide' Seaweed Sargassum horneri between Korean and Chinese Forms. Sustainability. 2020; 12(18), 7280
  7. Liu, F. Liu, X. Wang, Y. Jin, Z. Moejes, F.W. and Sun, S. Insights on the Sargassum horneri golden tides in the Yellow Sea inferred from morphological and molecular data. Limnol. Oceanogr. 2018 Apr; 63, 1762-1773. https://doi.org/10.1002/lno.10806
  8. Lee, B. J. Lee, S. M. Hyun, J. h. and Kim, Y. Y. Durability Performances of Concrete Produced with Recycled BioPolymer Based on Sargassum Honeri. J. Korean Recycl. Constr. Resour. Inst. 2019; 7, 445-451.
  9. Madhavaraj, L. Lim, H. D. Kim, K. M. Kim, D. H. and Han G. H. Influence of Sargassum horneri Mitigating Odorous Gas Emissions from Swine Manure Storage Facilities. Sustainability. 2020; 12, 7587.
  10. Kim, M. E. Jung, Y. C. Jung, I. Lee, H. W. Youn, H. Y. and Lee, J. S. Anti-inflammatory Effects of Ethanolic Extract from Sargassum horneri (Turner) C. Agardh on Lipopolysaccharide-Stimulated Macrophage Activation via NF-κB Pathway Regulation. Immunological Investigations. 2015; 44, 137-146 https://doi.org/10.3109/08820139.2014.942459
  11. Sanjeewa, K. K. A. Jayawardena, T. U. Lee, H. G. Herath, K. Jee, Y. and Jeon, Y. J. The protective effect of Sargassum horneri against particulate matter-induced inflammation in lung tissues of an in vivo mouse asthmamodel. Food Funct. 2019; 10, 7995-8004 https://doi.org/10.1039/C9FO02068C
  12. Rasin, A. B. Silchenko, A. S. Kusaykin, M. I. Malyarenko, O. S. Zueva, A. O. Kalinovsky, A. I. Airong, J. Surits, V.V. and Ermakova, S. P. Enzymatic transformation and anti-tumor activity of Sargassum horneri fucoidan. Carbohydrate Polymers. 2020; 246, 116635
  13. Shao, P. Liu, J. Chen, X. Fang, Z. and Sun, P. Structural features and antitumor activity of a purified polysaccharide extracted from Sargassum horneri. International Journal of Biological Macromolecules. 2015; 73, 124-130 https://doi.org/10.1016/j.ijbiomac.2014.10.056
  14. Lee, J. H. Kim, H. J. Jee, Y. Jeon, Y. J. and Kim, H. J. Antioxidant potential of Sargassum horneri extract against urban particulate matter-induced oxidation. Food Science and Biotechnology. 2020; 29, 855-865 https://doi.org/10.1007/s10068-019-00729-y
  15. Lee, G. Midorikawa, Y. Kuda, T. Harada, M. Fujita, S. Takahashi, H. and Kimura, B. In vitro antioxidant and anti-glycation properties of Sargassum horneri from golden tides on the South Korean coast and the effect on gut microbiota of mice fed a high-sucrose and low-fibre diet. Journal of Applied Phycology 2022; 34, 2211-2222 https://doi.org/10.1007/s10811-022-02756-5
  16. Kim, H. I. Kim, D. S. Jung, Y. Sung, N. Y. Kim, M. Han, I. J. Nho, E. Y. Hong, J. H. Lee, J. K. Boo, M. et al. Immune-Enhancing Effect of Sargassum hornerion Cyclophosphamide-Induced Immunosuppression in BALB/c Mice and Primary Cultured Splenocytes. Molecul es. 2022; 27, 8253
  17. Kim, D. S. Sung, N. Y. Park, S. Y. Kim, G. Eom, J. Yoo, J. G. Seo, I. R. Han, I. J. Cho, Y. B. and Kim, K.-A. Immunomodulating activity of Sargassum horneri extracts in RAW264. 7 macrophages. Journal of nutrition and health. 2018; 51, 507-514 https://doi.org/10.4163/jnh.2018.51.6.507
  18. Tomasi Jr, T.B. Tan, E.M. Solomon, A. and Prendergast, R. A. Characteristics of an immune system common to certain external secretions. The Journal of experimental medicine. 1965; 121, 101-124 https://doi.org/10.1084/jem.121.1.101
  19. Yatim, K. M. and Lakkis, F. G. A brief journey through the immune system. Clinical Journal of the American Society of Nephrology. 2015; 10, 1274-1281 https://doi.org/10.2215/CJN.10031014
  20. Gourbal, B. Pinaud, S. Beckers, G. J. Van Der Meer, J. W. Conrath, U. and Netea, M. G. Innate immune memory: An evolutionary perspective. Immunological reviews. 2018; 283, 21-40 https://doi.org/10.1111/imr.12647
  21. Cha, J. H. and Lim, E. M. Effects of Gardeniae fructus on cytokines in mouse macrophage. The Journal of Kore an Obstetrics and Gynecology. 2014; 27, 1-16 https://doi.org/10.15204/jkobgy2014.27.1.001
  22. Erwig, L. P. and Rees, A. J. Macrophage activation and programming and its role for macrophage function in glomerular inflammation. Kidney and Blood Pressure Research. 1999; 22, 21-25 https://doi.org/10.1159/000025905
  23. Jiang, M. H. Zhu, L. and Jiang, J. G. Immunoregulatory actions of polysaccharides from Chinese herbal medicine. Expert opinion on therapeutic targets. 2010; 14, 1367-1402 https://doi.org/10.1517/14728222.2010.531010
  24. Cant, A. and Cole, T. Infections in the immunocompromised. Adv Exp Med Biol. 2010; 659, 1-18 https://doi.org/10.1007/978-1-4419-0981-7_1
  25. Shortman, K.; Wu, L. Are dendritic cells end cells? Natur e Immunology. 2004; 5, 1105-1106. https://doi.org/10.1038/ni1104-1105
  26. Wang, C. Yu, X. Cao, Q. Wang, Y. Zheng, G. Tan, T.K. Zhao, H. Zhao, Y. Wang, and Y. Harris, D. C. H. Characterization of murine macrophages from bone marrow, spleen and peritoneum. BMC Immunology. 2013; 14, 6.
  27. Swanson K. V. Deng, M. Ting, J. P. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019 Aug;19(8):477-489. https://doi.org/10.1038/s41577-019-0165-0
  28. Mahla, R. S. Kumar, A. Tutill, H. J. Krishnaji, S. T. Sathyamoorthy, B. Noursadeghi, M. Breuer, J. Pandey, A.K. and Kumar, H. NIX-mediated mitophagy regulate metabolic reprogramming in phagocytic cells during mycobacterial infection. Tuberculosis. 2021; 126, 102046
  29. Nahrendorf, M. Hoyer, F. F. Meerwaldt, A. E. van Leent, M. M. Senders, M. L. Calcagno, C. Robson, P. M. Soultanidis, G. Perez-Medina, and C. Teunissen, A. J. Imaging cardiovascular and lung macrophages with the positron emission tomography sensor 64Cu-macrin in mice, rabbits, and pigs. Circulation: Cardiovascular Imaging. 2020; 13, e010586
  30. Sorimachi, K. Akimoto, K. Ikehara, Y. Inafuku, K. Okubo, A. and Yamazaki, S. Secretion of TNF-α, IL-8 and nitric oxide by macrophages activated with Agaricus blazei Murill fractions in vitro. Cell structure and function. 2001; 26, 103-108 https://doi.org/10.1247/csf.26.103
  31. Kim, Y. E. Lee, J. H. Sung, N. Y. Ahn, D. H. and Byun, E. H. A comparative study of the immuno-modulatory activities of ethanol extracts and crude polysaccharide fractions from Annona muricata L. Korean Journal of Food Science and Technology. 2017; 49, 453-458. https://doi.org/10.9721/KJFST.2017.49.4.453
  32. Yoon, T. J. Effect of water extracts from root of Taraxacum officinale on innate and adaptive immune responses in mice. The Korean Journal of Food And Nutrition. 2008; 21, 275-282.
  33. Izadpanah, K. Freyer, D. Weber, J.R. and Braun, J.S. Brain parenchymal TNF-α and IL-1β induction in experimental pneumococcal meningitis. Journal of Neuroimmunology. 2014; 276, 104-111 https://doi.org/10.1016/j.jneuroim.2014.08.625
  34. Tanaka, T. Narazaki, M. and Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harbor perspectives in biology. 2014; 6, a016295
  35. Simpson, R. J. Hammacher, A. Smith, D. K. Matthews, J. M. and Ward, L. D. Interleukin-6: Structure-function relationships. Protein science. 1997; 6, 929-955 https://doi.org/10.1002/pro.5560060501
  36. Kim, D. S. Sung, N. Y. Han, I. J. Lee, B. S. Park, S. Y. Nho, E. Y. Eom, J. Kim, G. and Kim, K. A. Splenocyte-mediated immune enhancing activity of Sargassum horneri extracts. Journal of Nutrition and Health. 2019; 52, 515-528 https://doi.org/10.4163/jnh.2019.52.6.515
  37. Hegazy, M. E. F. Hamed, A. R. Mohamed, T.A. Debbab, A. Nakamura, S. Matsuda, and H. Pare, P. W. Anti-inflammatory sesquiterpenes from the medicinal herb Tanacetum sinaicum. Rsc Advances. 2015; 5, 44895-44901 https://doi.org/10.1039/C5RA07511D
  38. Stachon, T. Latta, L. Seitz, B. and Szentmary, N. Hypoxic stress increases NF-κB and iNOS mRNA expression in normal, but not in keratoconus corneal fibroblasts. Graefe's Archive for Clinical and Experimental Ophthalmology. 2021; 259, 449-458 https://doi.org/10.1007/s00417-020-04900-8
  39. Li, X. Shang, B. Li, Y. n. Shi, Y. and Shao, C. IFNγ and TNFα synergistically induce apoptosis of mesenchymal stem/stromal cells via the induction of nitric oxide. Stem cell research & therapy. 2019; 10, 1-11. https://doi.org/10.1186/s13287-018-1105-9
  40. Berrios-Carcamo, P. Quezada, M. Quintanilla, M.E. Morales, P. Ezquer, M. Herrera-Marschitz, M. Israel, Y. and Ezquer, F. Oxidative stress and neuroinflammation as a pivot in drug abuse. A focus on the therapeutic potential of antioxidant and anti-inflammatory agents and biomolecules. Antioxidants. 2020; 9, 830.
  41. Coleman, J. W. Nitric oxide in immunity and inflammation. International immunopharmacology. 2001; 1, 1397-1406 https://doi.org/10.1016/S1567-5769(01)00086-8
  42. Chiou, W. F. Chou, C. J. and Chen, C. F. Camptothecin suppresses nitric oxide biosynthesis in RAW 264.7 macrophages. Life sciences. 2001; 69, 625-635 https://doi.org/10.1016/S0024-3205(01)01154-7
  43. Hibbs Jr, J.B. Taintor, R.R. Vavrin, Z. and Rachlin, E.M. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochemical and biophysical research communications. 1988; 157, 87-94 https://doi.org/10.1016/S0006-291X(88)80015-9
  44. Liu, Y. Shepherd, E. G. and Nelin, L. D. MAPK phosphatases-regulating the immune response. Nature Reviews Immunology. 2007; 7, 202-212. https://doi.org/10.1038/nri2035
  45. Corre, I. Paris, F. and Huot, J. The p38 pathway, a major pleiotropic cascade that transduces stress and metastatic signals in endothelial cells. Oncotarget. 2017; 8.
  46. Do, H. T. T. Bui, B.P. Sim, S. Jung, J. K. Lee, H. and Cho, J. Anti-Inflammatory and Anti-Migratory Activities of Isoquinoline-1-Carboxamide Derivatives in LPS-Treated BV2 Microglial Cells via Inhibition of MAPKs/NF-κB Pathway. International Journal of Molecular Sciences. 2020; 21, 2319.