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1 ORIGINAL ARTICLE Korean J Clin Lab Sci. 2018;50(2): pissn eissn Korean J Clin Lab Sci. Vol. 50, No. 2, June Inhibitory Effects of Zerumbone on MCP-1-Induced THP-1 Migration Sa Hyun Kim 1, Si Hyun Kim 1, Sung Ryul Ryu 1, Pyeongjae Lee 2, Cheol Moon 1 1 Department of Clinical Laboratory Science, Semyung University, Jecheon, Korea 2 Department of Natural Medicine Resources, Semyung University, Jecheon, Korea MCP-1 에의해유도된 THP-1 유주에미치는 Zerumbone 의영향 김사현 1, 김시현 1, 유성률 1, 이평재 2, 문철 1 1 세명대학교임상병리학과, 2 세명대학교자연약재학과 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. Key words: Migration, Monocyte, Monocyte chemoattractant protein 1, Zerumbone Corresponding author: Cheol Moon Department of Clinical Laboratory Science, Semyung University, 65 Semyung-ro, Jecheon 27136, Korea Tel: Fax: antigene@semyung.ac.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2018 The Korean Society for Clinical Laboratory Science. All rights reserved. Received: May 9, 2018 Revised: May 21, 2018 Accepted: May 22, 2018 서론단구는골수에서생성되는혈구로써선천면역계를구성하는주요세포다. 혈액을따라신체를순환하며탐식기능수행뿐아니라, 조직으로유주 (migration) 한후에는다양한대식세포혹은수지상세포로분화하여조직에침투한외부감염인자탐식, 조직항상성유지등의기능을발휘한다. 수지상세포는외부인자탐식후 T림프구에게항원을제시하여선천면역과후천면역 의매개자로써역할을수행한다. 그러므로, 단구의활성과기능에대한지식은면역반응전체를이해하는중요한시작점이된다. 나아가단구의활성과기능을강화혹은제어할수있는기전을통해외부침입인자에대한방어를강화하거나면역반응을조절할수있을것으로여겨진다. 최근에는단구와죽상동맥경화증 (atherosclerosis) 같은염증질환과의관계가연구되면서, 단구가만성ㆍ급성염증질환의매개자로인식되고있다 [1]. 야생생강의일종인 Zingiber zerumbet Smith의정유

2 178 Sa Hyun Kim et al. Zerumbone Inhibits THP-1 Migration (essential oil) 에포함되어있는주요성분인 zerumbone은혈액종양을포함한암세포죽음, 염증및활성산소감소등에기여할수있음이보고되었다 [2-4]. 또한면역세포들의증식과세포주기진행, 사이토카인의생성 발현에도효과를나타낸다고알려져있다 [5]. 이외에도간보호, 통증완화, 항동맥경화, 항미생물등 zerumbone의다양한생물학적기능이보고되었다 [6-9]. 특히, 신장상피세포암세포주를이용한이종이식모델연구를통해 zerumbone이암세포의증식, 생존, 혈관형성을억제하는기능이있음이보고되었다. 이와같은 zerumbone 의항암효능은 STAT3 의활성을저하시킴으로써나타난다 [10]. 또한, zerumbone 은 p53신호전달과정을활성화시켜췌장상피암세포의자가사멸을유도하였다 [11]. 이외에도간암, 위암, 피부암, 담도암등다양한암세포의세포자멸사유발, 전이방지효능을나타내는것으로알려져있다. 아울러, 항염증효능도보고되었는데, dextran sodium sulfate (DSS) 유발급성궤양성장염증세가 zerumbone 식이를통해호전되었으며 [12], 콜라겐유발관절염모델렛트에게 zerumbone 화합물을먹인후에증세가호전되었다는보고도있다 [13]. Zerumbone 은면역조절기능도지니고있음이보고되었다. 마우스의흉선세포와비장세포의증식이 zerumbone에의해더욱강화되었으며, 사람말초혈액단핵세포 (peripheral blood mononuclear cell, PBMC) 의증식역시 zerumbone에의해증가됨이보고되었다. 또한, zerumbone 이 G2/M 세포주기집중현상, 그리고, interleukin IL-2, IL-12 생성 / 분비증가를유발함이보고되었다 [5]. 아울러, SDF-1 에의해유도된 T세포주 Jurkat cell의유주현상이 zerumbone 에의해억제됨도보고되었다 [14]. 본연구는염증반응, 암세포를비롯한면역세포에다양한기능을나타내는 zerumbone 이단구의유주에어떠한영향을미치는지알아보고자진행되었다. 먼저 MCP-1에의해단구세포주 THP-1의유주가 MCP-1에의해유발되는것을확인하였으며, MCP-1에의해유발된유주는 zerumbone 에의해감소되었다. MCP-1 처리후감소하는 camp는 zerumbone에의해다시증가하였고, MCP-1에의해유도되었던 Erk 인산화는 zerumbone 에의해감소되었다. 이와같은결과를토대로 zerumbone 을통한단구의유주조절가능성을제시하고자한다. 재료및방법 1. 시약본연구에서사용된시약은 Zerumbone (Sigma-Aldrich, St. Louis, MO, USA) 와 Recombinant human CCL2 (MCP-1, BioLegend, San Diego, CA, USA) 이다. 2. 세포및세포배양사용한세포는사람단핵구세포주인 THP-1세포 (Korean Cell Line Bank, Seoul, Korea) 이다. 세포배양액은 Roswell Park Memorial Institute (RPMI) 1640 medium with L-glutamine (Lonza, Walkersvill, MD, USA) 에 10%(v/v) Fetal bovine serum (FBS) (Gibco, Grand Island, NY, USA), 1%(v/v) Penicillin/Streptomycin (Gibco, Grand Island, NY, USA), 1%(v/v) 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) (Welgene, Daegu, Korea), 1%(v/v) nonessential amino acid (Welgene, Daegu, Korea) 를첨가하여사용하였다. 배양은 37 C, 5% CO 2 조건을맞춘배양기를이용하여진행하였다. 3. Transwell migration assay 세포유주평가를위해 5 m pore size의 falcon cell culture inserts (Corning Co., NY, USA) 와 24 wells 짜리 falcon companion tissue culture plate (Corning Co., NY, USA) 를사용하였다. 실험은 migration buffer (RPMI 1640, 10 mm HEPES, ph 7.4, 0.1% BSA) 를이용하여진행하였고, 실험전세포는 migration buffer와함께 37 C, 5% CO 2 환경에서 overnight starvation 과정을거쳤다. 이후조건당 의 THP-1 세포를 200 L의 migration buffer에섞어 insert에넣고, underwell 에는 MCP-1 이첨가된 migration buffer 600 L 를넣었다. 준비된 insert를각 underwell 에삽입하고 37 C, 5% CO 2 환경에서배양하였다. 배양후에 insert를제거하고 underwell 로이동한세포들을 trypan blue를이용하여염색계수하였다. 4. camp 분비량측정 THP-1 세포주를 96 well plate에 cells/well 로 seeding 후조건별로 MCP-1 과 zerumbone 을처리하였다. 4시간후 96 well plate 를원심분리하고상층액을얻어 camp 측정용 ELISA kit (Cell Biolabs, San Diego, CA, USA) 를이용하여 camp를정량하였다. 제조사의측정방법에의거실험을진행하였다. 5. Western blot을통한단백질양및인산화정도분석 THP-1 세포주를 60 mm 배양접시에 cells/well로 seeding 후 MCP-1을 100 ng/ml 농도로, zerumbone을다양

Korean J Clin Lab Sci. Vol. 50, No. 2, June 2018 179 한농도 (1, 5, 10, 50 M) 로 2시간동안처리해주었다. PBS로 2회세척한후 lysis buffer 를이용해세포를용해시키고 19,000 g, 4 C에서 10분간원심분리하여단백질을추출하였다.

3 Korean J Clin Lab Sci. Vol. 50, No. 2, June 한농도 (1, 5, 10, 50 M) 로 2시간동안처리해주었다. PBS로 2회세척한후 lysis buffer 를이용해세포를용해시키고 19,000 g, 4 C에서 10분간원심분리하여단백질을추출하였다. 단백질의농도는 Lowry protein assay kit (Bio-Rad, Hercules, CA, USA) 를이용해정량하였고, 30 g의단백질을 10% acrylamide gel에서전기영동하여분리하였다. 분리된단백질은 nitrocellulose membrane에 transfer하고 5% skim milk를이용해실온에서 1시간 blocking 후각각 perk1/2, Erk, -actin 에특이적인 1차항체를희석하여 4 C에서 overnight 동안반응시켰다. 1차항체와반응이끝나면 3회세척후 2차항체와실온에서 2시간동안반응시키고, 다시 3회세척한후 ECL kit (Thermo, Waltham, MA, USA) 와반응시켜 X-ray film을이용해단백질의양및인산화정도를측정하였다. 6. 통계분석실험결과는 mean±sd 로표현하였다. ANOVA 를이용한 Student t-test를통해 P<0.05 이하인경우를유의한것으로판정하였다. 결과 1. MCP-1 에대한 THP-1 세포유주유도확인 Transwell assay system을통해다양한농도의 MCP-1 (0, 10, 50, 100, 200, 500 ng/ml) 처리후 THP-1의유주현상이유발됨을확인하였다 (Figure 1). 10 ng/ml의 MCP-1 처리시이미 5배이상의세포가 underwell로이동하였다. 100, 200 ng/ml 의 MCP-1 처리시유주세포수가약간상승하였고, 500 ng/ml 를처리했을경우에는감소하였다. 2. Zerumbone 에의한세포유주감소 MCP-1에의해유도된세포유주가 zerumbone 에의해감소하였다 (Figure 2). MCP-1과함께다양한농도 (10, 100, 500, 1000 nm) 의 zerumbone을동시에처리해주고 4시간후에 underwells 로이동한세포를계수하였다. 10 nm zerumbone 을처리해주었을때약 30% 의유주가감소했으며, 100 nm zerumbone 처리시 50% 이상의강한유주감소현상이나타났다. 500 nm zerumbone 처리시에는 100 nm zerumbone을처리했을때와비슷한정도의유주감소가나타났다. 3. Zerumbone 에의한 camp 발현강화 Zerumbone 및 MCP-1 처리시, camp 발현변화를발색반응측정원리에기반한 ELISA kit를이용하여측정 분석하였다 /well의 THP-1 세포를 zerumbone, MCP-1 단독처리혹은동시처리하여 4시간배양후원심분리하여상층액을얻었다. ELISA kit 제조사의실험방법에따라상층액내의 camp 농도를측정하였다. 어떠한시약으로도처리하지않았을때에는약 70 ng/ml 의 camp 가측정되었고, zerumbone 단독으로처리해주었을때에는 95 ng/ml로증가하였음을확인하였다. 반면에 MCP-1 단독으로처리해주었을때에는 camp 농도가 45 ng/ml 로감소하였다. MCP-1 단독처리에의한 camp의감소는 zerumbone을같이처리해주었을경우 80 ng/ml 정도로다시상승하였다 (Figure 3). Figure 1. THP-1 cell migration after MCP-1 treatmnet. THP-1 cells are incubated with various concentrations of MCP-1 (0, 10, 50, 100, 200, 500 ng/ml) for 4 hr. After incubation, the cells having migrated to the underwells were counted through trypan blue exclusion counting method. Values present mean±sd of three separate experiments (*P<0.05, **P<0.01). Figure 2. Inhibition of MCP-1 induced THP-1 migration by zerumbone. THP-1 cells are incubated with or without MCP-1 (100 ng/ml). The cells incubated with MCP-1 are simultaneously treated with various concentrations of zerumbone (0, 10, 100, 500, 1000 nm). After 4 hr of incubation, the cells of underwells were counted through trypan blue exclusion counting method. Values present mean±sd of three separate experiments (*P<0.05, **P<0.01).

4 180 Sa Hyun Kim et al. Zerumbone Inhibits THP-1 Migration Figure 3. Increase of camp expressions after treatment of zerumbone. THP-1 cells were incubated with zerumbone, MCP-1, and both reagents for 4 hr. After culturing, supernatant was obtained and camp concentration was measured. Values present mean±sd of three separate experiments (*P<0.05, **P<0.01). 4. Zerumbone 에의한 Erk 단백질의인산화감소 Erk 단백질의인산화정도는세포단독조건과 zerumbone 단독처리조건에서변화가없었으나, MCP-1을단독으로처리해주었을때증가하였다 (Figure 4). 그러나, zerumbone을 MCP-1 과동시에처리해주었을때에는다시세포단독조건혹은 zerumbone 단독조건과비슷한수준으로감소하였다. Erk 단백질자체의양은 MCP-1, zerumbone 단독처리혹은동시처리조건에서변화가없었다. 대조단백질인 -actin의양도의미있는변화를나타내지않았다. 고찰 단구는골수유래세포로써혈행을따라신체를돌다가조직과림프기관으로이동한다. 그곳에서대식세포혹은특이수지상세포들로분화하는특성을지닌다 [15]. 일상적인조건하에서조직으로이동한경우조직내대식세포수를보충해주는역할을하지만, 염증에대한반응으로조직으로이동한경우에는면역반응및염증반응에참여하는역할을하게된다. 단구와기타면역세포들의조직내이동현상은화학주성을일으키는케모카인 (chemokines) 을통해유발된다. 이화학주성은 G-단백결합케모카인수용체 (G protein-coupled chemokine receptors, GPCR) 와하부신호전달과정의활성화를통해진행된다. 염증이일어난조직으로이동하는단구들은 CC chemokine family receptor 2 (CCR2) 를많이발현하고있다. CCR2는염증반응중높게발현되는 MCP-1과결합하는수용체다 [16]. MCP-1에의해유발되는단구의유주현상은염증에대한적절한면역반응의발현을위해서중요한의미를지니지만, 여러염증질환의 Figure 4. Decrease of phosphrylation of Erk induced by MCP-1 after treatment of zerumbone. Changes in the phosphorylation patterns of Erk proteins after zerumbone and MCP-1 treatment were analyzed. Phosphorylation of Erk was increased by MCP-1 and was decreased when MCP-1 and zerumbone were simultaneously treated. Zerumbone treatment alone doesn t induce the phosphorylation. 진행에연관되어있다. 특히죽상동맥경화플라크형성및질병진행과단구간의관계는널리알려져있다 [1]. 이에단구의유주현상을조절하는방식으로죽상동맥경화증을예방 치료할가능성을생각해볼만하다. 이러한배경으로, 본연구는 zerumbone 이 MCP-1에의해유도된유주현상에미치는영향에대해알아보고자진행되었다. Zerumbone 은야생생강의일종인 Zingiber zerumbet Smith의주요생물활성성분이다. 실험에사용된 THP-1 세포는급성단핵구성백혈병세포에서유래한세포주로써단핵구의기능, 기능기전, 신호전달과정, 단핵구및대식세포기능등다양한단핵구관련연구에널리사용되고있다 [17]. 우선적으로, MCP-1 에의해 THP-1 의유주가발생하는지여부를알아보았다. 500 ng/ml 농도를제외하고, 처리해준모든농도의 MCP-1에의해유주현상이발생한것을확인하였다 (Figure 1). Transwell assay system 을사용하였고, 4시간배양후 underwell 로이동한 THP-1세포의수를 trypan blue를이용하여계수하였다. 가장강한유주현상을유발한 MCP-1의농도는 200 ng/ml 이지만, 오차범위와시약준비의용이성등을고려해이후의모든실험에 100 ng/ml 의농도를사용하였다. 다음으로 zerumbone 이유주현상에미치는영향을알아보기위해 transwell assay 중다양한농도의 zerumbone 을처리해주었다. MCP-1 (100 ng/ml) 을단독으로처리해준조건에서이동한세포의수를기준으로각농도별 zerumbone 처리후이동세포수의백분율을구하는방식으로정량하였다. MCP-1 과 zerumbone 을동시에처리해주었을경우, 처리한모든농도의 zerumbone 이유주현상을감소시켰음을확인하였다 (Figure 2). 10 nm의농도에서이미 30% 감소를나타냈으며, 100 nm 과 500 nm에서 50% 이상의강한감소를나타냈다.

5 Korean J Clin Lab Sci. Vol. 50, No. 2, June nm에서는유주현상이다소증가하는양상을관찰하였다. 이러한 zerumbone의유주현상감소기능이어떻게나타나는가를알아보기위해 cyclic adenosine monophosphate (camp) 분비량과 Erk 단백질의인산화변화양상을분석하였다. camp는 MCP-1의수용체인 CCR2 신호전달과정중중요한세포내 2차전달자중하나이다 [18]. camp 측정을위해 THP-1 세포를 zerumbone, MCP-1 각각단독으로처리해준조건, 두시약을동시에처리해준조건의배양액내 camp 농도를측정하였다 (Figure 3). 세포단독으로배양해주었을때에비해서, zerumbone 단독처리시배양액내 camp 의농도가 30% 이상증가하였다. MCP-1 단독처리시에는비슷한정도로감소한것을확인할수있었다. 그러나, MCP-1과 zerumbone 을동시에처리해주었을때 camp의농도는다시크게상승하였다. 이같은 camp의상승은 zerumbone 단독처리시정도는미치지못했으나, MCP-1 처리에의한 camp 감소효과를충분히극복하고남을정도의효과로보여진다. 다음으로, 대표적인 MCP-1 유발 THP-1 신호전달단백질 Erk의인산화경향변화를살펴보았다 [19]. Zerumbone 만처리해주었을때는아무것도처리하지않은상태의 Erk 인산화정도가관찰되었다 (Figure 4). MCP-1을단독으로처리해준경우에는분명한 Erk의인산화가관찰되었고, MCP-1과 zerumbone을동시에처리해준경우에는다시인산화정도가감소하였다. 본연구는 zerumbone이단핵구세포주인 THP-1 세포의유주현상을억제할수있음을시사한다. 유주현상유발을위해사용한 MCP-1 은염증반응시발현 분비되는대표적인케모카인으로써, 이미많은연구를통해죽상동맥경화시증가하여단구의이동과지방축적을유도한다는사실이알려져있다 [1]. 그러므로, 본연구결과는 zerumbone을이용한죽상동맥경화플라크형성및질환발전을감소가능성을보여준다. 이를위해우선사람의혈액에서분리한단구를이용하여 zerumbone 의기능을확인해야할필요가있다. 나아가동물질환모델을이용하여 zerumbone의효과를확인해야할것이다. 또한 zerumbone의작용기전을밝히기위해보다자세한생화학적연구가필요하다. MCP-1은염증과면역반응과정에서중요한기능을나타내는데, 특히죽상동맥경화증과연관된심혈관질환의초기, 후기에연관되어있는것으로알려져있다 [20]. MCP-1 단독처리후감소한 camp의농도는 zerumbone 처리를통해다시상승하였는데, 이에대한자세한기전연구가필요하다. camp에의해활성이증가되는 camp-dependent protein kinase A (PKA) 의활성을측정하는것도가능하다. 또한, camp와 Erk 인산화간의관계를보다명확하게분석해야하며, CCR2와같은 GPCR 신호전달과정의다른분자들의활성이 zerumbone 에의해어떠한영향을받는지분석해봐야할것으로생각된다. 요약 본연구는 zerumbone 이단구의유주에어떠한영향을미치는지알아보고자진행되었다. 단구는다양한염증질환의중요한매개자로인식되고있으며, 활성, 유주등단구의기능조절을통해염증질환을조절하는가능성이보고되고있다. 염증발생시증가하는케모카인인 MCP-1에의해단핵구세포주 THP-1의유주가유발되는것을확인하였다. 10 ng/ml의농도에서유주가발생하였으며, 100 ng/ml과 200 ng/ml의농도에서가장높은유주현상이나타났다. MCP-1에의해유발된 THP-1 유주는 zerumbone 존재시 50% 이상감소하였다. MCP-1 수용체인 CCR2 신호전달과정의중요 2차전달자인 camp 의배양액내농도는 zerumbone 단독처리시세포단독배양조건에비해증가하였으며, MCP-1 단독처리시에는의미있게감소하였다. 그러나, zerumbone 과 MCP-1을동시에처리했을때에는다시 camp의증가가관찰되었다. MCP-1 처리에의해일어나는 Erk 인산화도 zerumbone 과동시처리시감소하는결과를확인했다. 본연구는염증성질환에중요한매개자로인식되고있는단구의유주현상을조절하는 zerumbone 의가능성을보여준다. Acknowledgements: This paper was supported by the Semyung University Research Grant of Conflict of interest: None 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: Murakami A, Ohigashi H. Cancer-preventive anti-oxidants that attenuate free radical generation by inflammatory cells. Biol Chem. 2006;387: 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: 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:

6 182 Sa Hyun Kim et al. Zerumbone Inhibits THP-1 Migration 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: 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: 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: 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: 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: 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: 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: 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: 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: Moon C. Zerumbone's effects on jurkat cell proliferation and migration. Korean J Clin Lab Sci. 2015;47: Tacke F, Randolph GJ. Migratory fate and differentiation of blood monocyte subsets. Immunobiology. 2006;211: Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity. 2003;19: 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: Walther C, Ferguson SSG. Minireview: role of intracellular scaffolding proteins in the regulation of endocrine G protein-coupled receptor signaling. Mol Endocrinol. 2015;29: 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: Bianconi V, Sahebkar A, Atkin SL, Pirro M. The regulation and importance of monocyte chemoattractant protein-1. Curr Opin Hematol. 2017;24:1-8.

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untitled 182 Cheol Moon. Zerumbone's Effects on T Cell Physiology ORIGINAL ARTICLE Korean J Clin Lab Sci. 2015, 47(4):182-187 http://dx.doi.org/10.15324/kjcls.2015.47.4.182 pissn 1738-3544 eissn 2288-1662 Zerumbone