• Title/Summary/Keyword: mediators

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An Analysis of the Study Tendency on Rheumatoid Arthritis -Focusing on Domestic Theses for a Degree and Journal Since 2004- (류마토이드 관절염의 연구동향에 대한 소고(小考) -2004년 이후의 국내 학위논문 및 학회지 논문을 중심으로-)

  • Choi, Yong-Hun;Yoon, Il-Ji
    • Journal of Korean Medicine Rehabilitation
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    • v.19 no.2
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    • pp.125-156
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    • 2009
  • Objectives : To research the trend of studies related to rheumatoid arthritis and to indicate the hereafter direction for its study in oriental medicine and its treatment. Methods : I reviewed 75 domestic oriental medical journals, and 50 medical journals about rheumatoid arthritis published after 2004, and comparative analysis was made. And these theses were classified by college, year, field of study, subject. Results : The following are the results of this study. 1. Classified by oriental medical college, Dae-jeon college published the most theses, followed by Dong-guk, Kyung-hee, Se-myung and Dong-shin college. Han-yang college published the most theses among college of medicine. 2. Classified by type of thesis, experimental theses(70 pieces, 94%) showed higher rate than that of clinical theses(4 pieces, 5%) in oriental medical studies. However, in medical studies, clinical theses(34 pieces, 68%) showed higher rate than that of experimental theses(15 pieces, 30%). 3. Analyzed by subject, the most dealt subject in oriental medicine was herb medication, followed by herbal acupuncture, single herb, electroacupuncture, sasang & gene, acupuncture & moxibustion, complex accordingly. The most dealt subject in medical clinical journals was standards of diagnosis & prognosis, followed by medication, gene analysis, pathogenesis, clinical pattern, operative treatment and complication accordingly. 4. In theses related to herb medication, most of the subject was to evaluate anti-inflammatory and immunoregulatory effects of herb medication with geopungseup, jibitong, hwalhyeolgeoer function. The tendency of experimental methods was focusing on understanding anti-inflammatory and immunoregulatory mechanisms through molecular biologic methods by analyzing cytokine and gene. 5. Most of theses related to herbal acupuncture were experimental studies verifying ant-inflammatory and immnoregulatory effects through methods observing change of cytokine and immunoregulatory factors. Regarding remedies for herbal acupuncture, Ulmus davidiana Planch was most preferred, followed by bee venom. 6. In theses related to single herb, Boik-yak was most prefered, followed by Geopungseup-yak and Hwalhyeolgeoer-yak. Regarding methods of research, there were tendency of shifting from methods verifying travail, anti-inflammatory and anti-pyretic effects through a test of behavior, morphometry, serology and temperature measurement of the rectum and the skin into verifying anti-inflammatory and immunoregulatory effects through observing inflammatory cytokine in the joint and cells of spleen. 7. In theses related to electroacupuncture, ST36 and adjuvant were most preferred as acupoints and induced factor. The tendency of experimental methods was turning from verifying mechanism of travail effect to analyzing inflammation and pain inducing factors. 8. Diverse medical clinical studies were published. Subjects such as diagnosis and prognosis, medication, gene analysis, clinical pattern, operational treatment, complication and pathogenesis were published. Especially, studies about standards of early diagnosis, and research on possible parallel medications with methotrexate were actively inquired. 9. Most of theses related to medical experimental studies was about mediators and receptors related to inflammatory induction and osteoclasia mechanism. Also, it was presented blockage of them can be effective on rheumatoid arthritis. Conclusions : The oriental medicine studies have merit in its diversity of treatment, but it clinical studies is lacking compared to experimental studies. Also, more diversity of subjects is necessary. Therefore, complementary measures are needed. Hereafter, oriental medicine research about rheumatoid arthritis needs more clinical research verifying the effectiveness and safety in clinical field. Also, we require oriental medical standard of diagnosis and researches on pathological generation which would make early checkup and prognosis possible.

Effect of PLA2 Inhibitor Rutin on Endotoxin-Induced Acute Lung Injury (내독소로 유도된 급성폐손상에서 PLA2의 억제제인 Rutin의 효과)

  • Kim, Seong-Eun;Lee, Young-Man;Park, Won-Hark
    • Applied Microscopy
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    • v.34 no.1
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    • pp.31-42
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    • 2004
  • Acute respiratory distress syndrome (ARDS) is a kind of acute lung injury characterized by inflammatory disruption of alveolar-capillary barrier and notorious for its high mortality. Neutrophils cause cell damage through the production of free radicals, inflammatory mediators, and proteases in ARDS. $PLA_2$ might serve a primary regulatory role in the activation of neutrophils. This present study was performed to elucidate the effect of rutin known as $PLA_2$ inhibitor on ARDS induced by endotoxin. Endotoxin had increased lung myeloperoxidase (MPO) activity, BAL (bronchoalveolar lavage) protein content, numbers of neutrophils in BALF (bronchoalveolar lavage fluid) compared with those of control rat (p<0.001). In addition, histological evidence of lung injury was correlated with neutrophil influx into alveolar space and cerrous perhydroxide granules were found in lining of endothelial cell, alveolar type I, II cells. In contrast, pretreated group of rutin had significantly decreased all of the parameters (p<0.001). These data suggest that inhibition of $PLA_2$ is one step approach that block the process of ARDS. Accordingly, we conclude that rutin can be used as the prophylactic agent for ARDS on the bases of these experimental results.

Antioxidant activity and suppression of pro-inflammatory mediator of Corni fructus extracts in activated RAW 264.7 macrophage (산수유(Corni fructus) 분획 추출물의 항산화 활성 및 RAW 264.7 대식세포에서 염증매개물질 억제 효과)

  • Kim, Ye Jin;Son, Dae-Yeul
    • Food Science and Preservation
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    • v.23 no.6
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    • pp.876-882
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    • 2016
  • The antioxidant and anti-inflammatory effects of Corni fructus extracts (CEF, EtOAc extraction; CBF, buthanol extraction; CWF, water extraction) were investigated. The total phenolics of CEF (173.3 mg TAE/g) were significantly higher than those of CWF (26.7 mg TAE/g) and CBF (94.8 mg TAE/g). DPPH and ABTS free radical scavenging activity of CEF (DPPH: $RH_{50}$; $25.1{\mu}g/mL$, ABTS: $RC_{50}$; $36.1{\mu}g/mL$) showed even higher than that of BHA and ${\alpha}-tocopherol$ used as positive control. All three Corni fructus extracts in the concentration of $1{\sim}100{\mu}g/mL$ were effective inhibitors of NO and prostaglandin $E_2$ ($PGE_2$). NO production was inhibited 71.3~92.2% by CEF, 76.8~85.5% by CBF and 74.4~96.9% by CWF, respectively. CEF, CBF and CWF ($1{\sim}100{\mu}g/mL$) inhibited also pro-inflammatory cytokines like $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 very effectively. $TNF-{\alpha}$ was inhibited up to 51.2% by CWF and $IL-1{\beta}$ was inhibited up to 67.1% by CEF. IL-6 was best inhibited by CEF up to 58.9%. This study suggested the potential of Corni fructus for use as an excellent antioxidant substance and inflammatory inhibiting mediators. Therefore CEF, CBF and CWF Corni fructus extracts may be used for therapeutic approach to various inflammatory diseases.

Induction of Phase I, II and III Drug Metabolism/Transport by Xenobiotics

  • Xu Chang Jiang;Li Christina YongTao;Kong AhNg Tony
    • Archives of Pharmacal Research
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    • v.28 no.3
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    • pp.249-268
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    • 2005
  • Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coordinated fashion, and provides an important mean to protect the body from xenobiotics insults. It appears that in general, exposure to phase I, phase II and phase III gene inducers may trigger cellular 'stress' response leading to the increase in their gene expression, which ultimately enhance the elimination and clearance of these xenobiotics and/or other 'cellular stresses' including harmful reactive intermediates such as reactive oxygen species (ROS), so that the body will remove the 'stress' expeditiously. Consequently, this homeostatic response of the body plays a central role in the protection of the body against 'environmental' insults such as those elicited by exposure to xenobiotics.

Effects of 20(S)-Protopanaxadiol and 20(S)-Protopanaxatriol on the Inflammatory Mediators Release from the Activated Mast Cells (20(S)-Protopanaxadiol 및 20(S)-Protopanaxatriol이 활성화된 비만세포로부터의 염증 매개체 유리에 미치는 영향)

  • Ro, Jai-Youl;Han, Yong-Nam;Choi, Kwang-Tae;Lee, Chang-Ho
    • Journal of Ginseng Research
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    • v.33 no.4
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    • pp.316-323
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    • 2009
  • Ginseng saponins have various pharmacological effects on the immune system. 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT) are the species of ginseng saponin metabolites that are formed by human intestinal bacteria and detected in circulation. The effects of PPD and PPT on the inflammatory mediator release from the activated mast cells were tested. Histamine release was evaluated in activated guinea pig lung mast cells, and the secretion of interleukin-4 (IL-4), interleukin-8 (IL-8), and the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) was assessed in an HMC-1 cell after treating it with ginseng saponin metabolites. The results are as follows. PPT, at its maximum concentration of $100\;{\mu}M$, completely abolished the secretion of IL-4 from the PMA-stimulated HMC-1 cell. It also inhibited IL-8 secretion from the same cells by about 40-50% of the PMA-treated DMSO control. PPD, at its maximum concentration of $100\;{\mu}M$, showed a tendency to induce histamine release from the guinea pig lung mast cells. It inhibited the secretion of IL-4 (by 89% of the PMA-treated DMSO control) in the PMA-stimulated HMC-1 cell, but did have a significant effect on the IL-8 release from the same cell. Both PPD and PPT showed no effects, however, on the release of TNF-${\alpha}$ from the PMA-stimulated HMC-1 cell. These results suggest that PPD and PPT are from the ginseng metabolites that are responsible for the immunomodulating activity of ginseng extracts when they are taken orally.

Beneficial Effect of Korea Red Ginseng on Halitosis; Attenuation of H2S Induced Inflammatory Mediators and cystathionine γ-lyase Expression (고려홍삼의 구강악취 억제기능; H2S 생성에 따른 염증매개 유전자 및 cystathionine γ-lyase의 약화기능)

  • Choi, Ki-Seok;Lee, So-Jung;Lee, Jeong-Sang;Hong, Kyung-Sook;Kim, Jeong-Gon;Kim, Yoon-Jae;Hahm, Ki-Baik
    • Journal of Ginseng Research
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    • v.33 no.4
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    • pp.367-377
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    • 2009
  • Halitosis is a generally accepted marker of diseases in the oral cavity and of systemic and gastrointestinal disorders. Based on these authors' previous findings (that (1) there is a close association between H. pylori infection and halitosis; (2) Korea red ginseng may suppress the colonization of H. pylori, fight H. pylori-induced cytotoxicity, and impose significant anti-inflammatory actions in patients with chronic gastritis; and (3) H. pylori infection is linked with the generation of significant levels of volatile sulfur compounds (VSCs), and the levels of VSCs correlate significantly with H. pylori-associated mucosal damages), in the current study, the authors documented the molecular mechanisms of Korea red ginseng's efficacy in ameliorating halitosis. When the RAW 264.7 cells were treated with the $H_2S$ releasing compound NaHS, the mRNA expression of cystathionine ${\gamma}$-lyase (CSE), IL-6, COX-2, and iNOS were more significantly induced compared with the vehicle-treated group. The cytoskeletal components of ezrin's and moesin's mRNA expressions were elevated by NaHS treatment accompanied by the activation of MAPK, p38, and ERK. Korea red ginseng pretreatment reduced both the NaHS-induced CSE expression and the proinflammatory genes (e.g., IL-6, COX-2, and iNOS) in a concentration-dependent manner. The ERM expression and the phosphorylation of p38 were also significantly reduced by Korea-red-ginseng pretreatment. Overall, Korea red ginseng pretreatment imposed significant anti-inflammatory effects through the downregulation of the NaHS-triggered proinflammatory gene expression, CSE, and ERM mRNA expression. Korea red ginseng could thus be said to be a key remedy of halitosis and to be effective in relieving gastric inflammation.

Inhibitory Effects of Extracts from Arabis glabra on Lipopolysaccharide Induced Nitric Oxide and Prostaglandin E2 Production in RAW264.7 Macrophages (RAW264.7 대식세포에서 장대나물 추출물의 Nitric oxide 및 Prostaglandin E2생성 저해효과)

  • Nam, Jung-Hwan;Seo, Jong-Taek;Kim, Yul-Ho;Kim, Ki-Deog;Yoo, Dong-Lim;Lee, Jong-Nam;Hong, Su-Young;Kim, Su-Jeong;Sohn, Hwang-Bae;Kim, Hyun-Sam;Kim, Bo-Sung;Shin, Ji-Sun;Lee, Kyung-Tea;Park, Hee-Jhun
    • Korean Journal of Plant Resources
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    • v.28 no.5
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    • pp.568-573
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    • 2015
  • Arabis glabra is a localized common rhizomatous flowering plant, This plant is often used in Korean traditional systems of medicine as a remedy for blood cleaning, detoxification, abscess, gastrospasm, arthritis, contraction and diarrhea. Generally drugs that are used for arthritis have antinociceptive and anti-inflammatory properties. However, validity of the anti-inflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the anti-inflammatory potential of A. glabra using the ethanolic extract and its sub-fractions. To evaluate the anti-inflammatory effects, we examined the inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) on RAW 264.7macrophages. Our results indicated that hexane and chloroform fraction significantly inhibited the LPS-induced NO and PGE2 production in the cells. The hexane fraction inhibitory activity for NO tests with IC50 values showed in 21.0 ㎍/㎖. The chloroform fraction inhibitory activity for PGE2 tests with IC50 values showed in 18.0 ㎍/㎖. These efficacy are expected to be able to present the potential for the development of health functional food for the prevention inflammatory diseases because it has sufficient preventive medical possibilities. Further, it is determined that it is necessary to further study the mechanism of cytokine and protein expression associated with inflammation.

Anti-inflammatory Effects on 80% Ethanol Extract and Ethyl Acetate Fraction of Acrosorium yendoi Yamada in Murine Macrophage RAW 264.7 Cells (Murine Macrophage RAW 264.7 세포에서 누은분홍잎(Acrosorium yendoi Yamada)의 추출물과 에틸아세테이트 분획물에 대한 항염증 효과)

  • Ko, Chang-Sik;Hyun, Woo-Cheol;Kim, Ji-hyun;Ko, Yeong-Jong;Song, Sang Mok;Ko, Mi-Hee;Lee, Jong-Chul;Kim, Chang-Sook;Yoon, Weon-Jong
    • Korean Journal of Plant Resources
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    • v.28 no.5
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    • pp.574-581
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    • 2015
  • This study describes a preliminary evaluation of the anti-inflammatory activity of Acrosorium yendoi Yamada extracts. A. yendoi Yamada was extracted using 80% ethanol and then fractionated sequentially with n-hexane, ethyl acetate and butanol. To screen for anti-inflammatory agents effectively, we first examined the inhibitory effect of 80% EtOH extract and solvent fractions of A. yendoi Yamada on the production of pro-inflammatory factors and cytokines stimulated with lipopolysaccharide. In addition, we examined the inhibitory effect of 80% EtOH extract and solvent fractions of A. yendoi Yamada on pro-inflammatory mediators (NO, iNOS, PGE2, and COX-2) in RAW 264.7 cells. In the sequential fractions of n-hexane and EtOAc inhibited the NO and PGE2 production and the protein level of iNOS and COX-2, and protein expression of pro-inflammatory cytokines (TNF-α, and IL-6). These results suggest that A. yendoi Yamada may have significant effects on inflammatory factors and may be provided as possible anti-inflammatory therapeutic seaweed.

Anti-Inflammatory Effect of Ethanol Extract from Onion (Allium cepa L.) Peel on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells and Mice Ears (LPS로 유도된 RAW 264.7 세포와 마우스 귀 조직에 대한 양파(Allium cepa L.) 껍질 에탄올 추출물의 항염증 효과)

  • Ahn, Na-Kyung;Kang, Bo-Kyeong;Kim, Koth-Bong-Woo-Ri;Kim, Min-Ji;Bae, Nan-Young;Park, Ji-Hye;Park, Sun-Hee;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.11
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    • pp.1612-1620
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    • 2015
  • Inflammation is a complex process involving a variety of immune cells, which defend the body from harmful stimuli. However, pro-inflammatory cytokines and inflammatory mediators can also exacerbate diseases such as cancer. Onion peel contains several phenolic compounds, including quercetin at an amount 20 times greater in peel than edible flesh. Therefore, in this study, the anti-inflammatory effects of onion peel ethanol extract (OPEE) were investigated lipopolysaccharide-induced inflammatory response. In our results, NO production decreased in a dose-dependent manner. Secretion of IL-6, $TNF-{\alpha}$, and $IL-1{\beta}$ was suppressed by 44%, 53%, and 60% respectively, at $100{\mu}g/mL$. Moreover, OPEE also suppressed expression of COX-2, iNOS, $NF-{\kappa}B$, and MAPKs in a dose-dependent manner. Formation of mice ear edema was reduced at the highest dose tested compared to the control, and reduction of ear thickness was observed in the histological analysis as well. In the acute toxicity test, no morality was observed in mice administered 5,000 mg/kg body weight of OPEE over a 2-week observation period. These results suggest that OPEE may have significant effects on inflammatory factors and be a potential anti-inflammatory material.

Co-Culture Model Using THP-1 Cell and HUVEC on AGEs-Induced Expression of Cytokines and RAGE (THP-1 Cell과 HUVEC을 이용한 Co-Culture Model System에서 최종당화산물에 의한 Cytokines와 RAGE 발현)

  • Lee, Kwang-Won;Lee, Hyun-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.3
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    • pp.385-392
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    • 2011
  • Although monoculture methods have been remarkably useful due to their simplicity, they have serious limitation because of the different types of cells communication with each other in many physiological situations. We demonstrated levels of markers of endothelial dysfunction such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$) as well as stimulation of receptor of advanced glycation endproducts (AGEs) on monoand co-culture system such as only monocyte (THP-1) cultivation system, only endothelial cell (HUVEC) cultivation system, and co-cultivation system of THP-1 and HUVEC. The mRNA levels of TNF-$\alpha$ and IL-1$\beta$ on HUVEC increased by the co-culture with monocyte after 4 hr at 100 ${\mu}g/mL$ glyceraldehyde-AGE. The secreted protein contents into medium of TNF-$\alpha$ and IL-1$\beta$ increased after 8 hr approximately 2~2.5 times compared to mono-cultivation. In contrast, the mRNA level of receptor of AGE (RAGE) was relatively insensitive on the co-culture system. The mediators by which monocytes activate endothelial cell have not been fully elucidated. In this study we confirmed production of soluble cytokines such as TNF-$\alpha$ and IL-1$\beta$ by monocytes. Use of monocyte conditioned medium, which contains both cytokines, can activate endothelial cell.