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Inhibitory Effects of Zerumbone on MCP-1-Induced THP-1 Migration

MCP-1에 의해 유도된 THP-1 유주에 미치는 Zerumbone의 영향

  • Kim, Sa Hyun (Department of Clinical Laboratory Science, Semyung University) ;
  • Kim, Si Hyun (Department of Clinical Laboratory Science, Semyung University) ;
  • Ryu, Sung Ryul (Department of Clinical Laboratory Science, Semyung University) ;
  • Lee, Pyeongjae (Department of Natural Medicine Resources, Semyung University) ;
  • Moon, Cheol (Department of Clinical Laboratory Science, Semyung University)
  • 김사현 (세명대학교 임상병리학과) ;
  • 김시현 (세명대학교 임상병리학과) ;
  • 유성률 (세명대학교 임상병리학과) ;
  • 이평재 (세명대학교 자연약재학과) ;
  • 문철 (세명대학교 임상병리학과)
  • Received : 2018.05.09
  • Accepted : 2018.05.22
  • Published : 2018.06.30

Abstract

This study examined the effects of zerumbone on monocyte migration. Monocytes are recognized as important mediators of various inflammatory diseases, and the possibility of controlling inflammatory diseases by regulating the monocyte functions, such as activity and mobility, has been reported. MCP-1, which is a chemokine with levels that increase upon inflammation, causes the migration of the monocyte cell line, THP-1. Migration occurred at a concentration of 10 ng/mL MCP-1, and the highest migration occurred at 100 ng/mL and 200 ng/mL. MCP-1-induced THP-1 migration decreased by more than 40% in the presence of zerumbone. The concentration of cAMP, an important secondary messenger of the CCR2 signaling pathway, the MCP-1 receptor, was increased in the culture medium after a zerumbone treatment. The concentrations of cAMP decreased significantly under the MCP-1 treatment condition only. On the other hand, an increase in cAMP was observed when zerumbone and MCP-1 were treated simultaneously. Erk phosphorylation induced by an MCP-1 treatment was also found to decrease with the zerumbone treatment. This study introduces the possibility of controlling inflammatory diseases through the function of zerumbone, which regulates the migration of monocytes.

본 연구는 zerumbone이 단구의 유주에 어떠한 영향을 미치는지 알아보고자 진행되었다. 단구는 다양한 염증 질환의 중요한 매개자로 인식되고 있으며, 활성, 유주 등 단구의 기능 조절을 통해 염증 질환을 조절하는 가능성이 보고 되고 있다. 염증 발생 시 증가하는 케모카인인 MCP-1에 의해 단핵구 세포주 THP-1의 유주가 유발되는 것을 확인하였다. 10 ng/mL의 농도에서 유주가 발생하였으며, 100 ng/mL과 200 ng/mL의 농도에서 가장 높은 유주 현상이 나타났다. MCP-1에 의해 유발된 THP-1 유주는 zerumbone 존재 시 50% 이상 감소하였다. MCP-1 수용체인 CCR2 신호전달 과정의 중요 2차 전달자인 cAMP의 배양액 내 농도는 zerumbone 단독 처리 시 세포 단독 배양 조건에 비해 증가하였으며, MCP-1 단독 처리 시에는 의미있게 감소하였다. 그러나, zerumbone과 MCP-1을 동시에 처리했을 때에는 다시 cAMP의 증가가 관찰되었다. MCP-1 처리에 의해 일어나는 Erk 인산화도 zerumbone과 동시 처리 시 감소하는 결과를 확인했다. 본 연구는 염증성 질환에 중요한 매개자로 인식되고 있는 단구의 유주 현상을 조절하는 zerumbone의 가능성을 보여준다.

Keywords

References

  1. Gautier EL, Jakubzick C, Randolph GJ. Regulation of the migration and survival of monocyte subsets by chemokine receptors and its relevance to atherosclerosis. Artherioscler Thromb Vasc Biol. 2009;29:1412-1418. https://doi.org/10.1161/ATVBAHA.108.180505
  2. Murakami A, Ohigashi H. Cancer-preventive anti-oxidants that attenuate free radical generation by inflammatory cells. Biol Chem. 2006;387:387-392.
  3. Sulaiman MR, Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Tasrip NA, et al. Anti-inflammatory effect of zerumbone on acute and chronic inflammation models in mice. Fitoterapia. 2010;81:855-858. https://doi.org/10.1016/j.fitote.2010.05.009
  4. Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Ming OH, Khalid S, et al. Zerumbone-induced antinociception: involvement of the L-arginine-nitric oxide-cGMP -PKC-K+ ATP channel pathways. Basic Clin Pharmacol Toxico. 2011;l108:155-162.
  5. Keong YS, Alitheen NB, Mustafa S, Abdul Aziz S, Abdul Rahman M, Ali AM. Immunomodulatory effects of zerumbone isolated from roots of Zingiber zerumbet. Pak J Pharm Sci. 2010;23:75-82.
  6. Kitayama T, Iwabuchi R, Minagawa S, Shiomi F, Cappiello J, Sawada S, et al. Unprecedented olefin-dependent histidinekinase inhibitory of zerumbone ring-opening material. Bioorg Med Chem Lett. 2004;23:5943-5946.
  7. Eguchi A, Kaneko Y, Murakami A, Ohigashi H. Zerumbone suppresses phorbol ester-induced expression of multiple scavenger receptor genes in THP-1 human monocytic cells. Biosci Biotechnol Biochem. 2007;71:935-945. https://doi.org/10.1271/bbb.60596
  8. Sulaiman MR, Perimal EK, Zakaria ZA, Mokhtar F, Akhtar MN, Lajis NH, et al. Preliminary analysis of the antinociceptive activity of zerumbone. Fitoterapia. 2009;80:230-232. https://doi.org/10.1016/j.fitote.2009.02.002
  9. Taha MM, Abdul AB, Abdullah R, Ibrahim TA, Abdelwahab SI, Mohan S. Potential chemoprevention of diethylnitrosamineinitiated and 2-acetylaminofluorene-promoted hepatocarcinogenesis by zerumbone from the rhizomes of the subtropical ginger (Zingiber zerumbet). Chem Biol Interact. 2010;186:295-305. https://doi.org/10.1016/j.cbi.2010.04.029
  10. Shanmugam MK, Rajendran P, Li F, Kim C, Sikka S, Siveen KS, et al. Abrogation of STAT3 signaling cascade by zerumbone inhibits proliferation and induces apoptosis in renal cell carcinoma xenograft mouse model. Mol Carcinog. 2015;54:971-985. https://doi.org/10.1002/mc.22166
  11. Zhang S, Liu Q, Liu Y, Oiao H, Liu Y. Zerumbone, a Southeast Asian ginger sesquiterpene, induced apoptosis of pancreatic carcinoma cells through p53 signaling pathway. Evid Based Complement Alternat Med. 2012;2012:936030.
  12. Murakami A, Hayashi R, Tanaka T, Kwon KH, Ohigashi H, Safitri R. Suppression of dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger sesquiterpene, and nimesulide: separately and in combination. Biochem Pharmacol. 2003;66:1253-1261. https://doi.org/10.1016/S0006-2952(03)00446-5
  13. Murakami A, Song M, Katsumata S, Uehara M, Suzuki K, Ohigashi H. Citrus nobiletin suppresses bone loss in ovariectomized ddY mice and collagen-induced arthritis in DBA/1J mice: possible involvement of receptor activator of NF-kappaB ligand (RANKL)-induced osteoclastogenesis regulation. Biofactors. 2007;30:179-192. https://doi.org/10.1002/biof.5520300305
  14. Moon C. Zerumbone's effects on jurkat cell proliferation and migration. Korean J Clin Lab Sci. 2015;47:182-187. https://doi.org/10.15324/kjcls.2015.47.4.182
  15. Tacke F, Randolph GJ. Migratory fate and differentiation of blood monocyte subsets. Immunobiology. 2006;211:609-618. https://doi.org/10.1016/j.imbio.2006.05.025
  16. Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity. 2003;19:71-82. https://doi.org/10.1016/S1074-7613(03)00174-2
  17. Chanput W, Mes J, Vreeburg RAM, Savelkoul HFJ, Wichers HJ. Transcription profiles of LPS-stimulated THP-1 monocytes and macrophages: a tool to study inflammation modulating effects of food-derived compounds. Food & Function. 2010;1:254-261. https://doi.org/10.1039/c0fo00113a
  18. Walther C, Ferguson SSG. Minireview: role of intracellular scaffolding proteins in the regulation of endocrine G protein-coupled receptor signaling. Mol Endocrinol. 2015;29:814-830. https://doi.org/10.1210/me.2015-1091
  19. Carmen Jimenez-Sainz M, Fast B, Mayor F, Aragay AM. Signaling pathways for monocyte chemoattractant protein 1-mediated extracellular signal-regulated kinase activation. Mol Pharmacol. 2003;64:773-782. https://doi.org/10.1124/mol.64.3.773
  20. Bianconi V, Sahebkar A, Atkin SL, Pirro M. The regulation and importance of monocyte chemoattractant protein-1. Curr Opin Hematol. 2017;24:1-8. https://doi.org/10.1097/MOH.0000000000000304

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