• Title/Summary/Keyword: MMP-2/9

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Study on the Anti-cancer, Anti-metastasis and Immune response improvement of Aqua-acupuncture with Cistanches Herba infusion solution (육종용약침의 항암작용(抗癌作用) 및 면역효과(免疫效果)에 대(對)한 실험적(實驗的) 연구(硏究))

  • Lee, Eun-Yong;Lee, Byung-Ryul
    • Journal of Acupuncture Research
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    • v.17 no.1
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    • pp.251-286
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    • 2000
  • To study the effects of anti-cancer, anti-metastasis and immune response improvement of aqua-acupuncture with Cistanches Herba infusion solution, we used Cistanches Herba infusion solution(taken by water-alcohol method) put into Chung-wan(CV12) and Chok-Samni(S36) of BALB/c or C57BL/6 which are corresponding to human body. We observed the cytotoxicity, the effect on the expression of MMP-9 gene, the ability to control cancer cell proliferation, change of body weight, surviving number, MST, ILS, changes in amount of WBC, RBC, PLT, total protein, creatinine, glucose and LDH, weight of spleen, number of pulmonary colony, histological analysis on tissue metastasis of lung and liver, splenic cell proliferation, the expression of cytokine gene, the number of $CD4^+$, $CD8^+$, $CD19^+$ and NK cell, and concluded like this. The results were obtained as follows : 1. The cytotoxicity about B16-F10 cell line of $2^0$, $2^{-1}$, $2^{-2}$, $2^{-5}$ diluent groups in Cistanches Herba infusion solution treatment was inhibited significantly, compared with control group. 2. The cytotoxicity about HT1080 cell line of $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-5}$, $2^{-8}$ diluent groups in Cistanches Herba infusion solution treatment was inhibited significantly, compared with control group. 3. The effect on expression of MMP-9 gene was decreased in all the sample groups, compared with control group. 4. The effect on the control-ability on the cancer cell proliferation showed cytotooicity significantly in $2^0$, $2^{-1}$, $2^{-2}$, $2^{-3}$, $2^{-4}$, $2^{-5}$ diluent groups. 5. S-180 cancer cell line transplants in BALB/c mice were inhibited significantly in weight increase in all the sample groups, compared with control group. The surviving number increased in almost sample groups, except one group put into Chok-Samni(S36) with 20% Cistanches Herba infusion solution treatment group that showed same number of the control group. 6. S-180 cancer cell line transplants in BALB/c mice showed high MST and ILS significantly in almost sample groups, compared with control group. But one group put into Chok-Samni(S36) with 20% Cistanches Herba infusion solution treatment group showed low MST and ILS than control group. 7. The sample group injected in vein with B16-F10 cancer cell line in C57BL/6 mice showed increased ILS compared with control group significantly in anti-metastasis test. 8. The sample group injected in vein with B16-F10 cancer cell line in C57BL/6 mice were increased significantly in the number of WBC and glucose, and decreased significantly in the amount of LDH, compared with control group. However, there's no significant increase or decrease in number of RBC, PLT, total protein and creatinine. 9. We couldn't find any significant relation in spleen weight of the sample group. 10. In pulmonary colony, sample group was decreased significantly, compared with control group. 11. Histological analysis of sample group inhivited compared with that of control group in both of lung and liver. 12. In immune system, all the sample groups showed having more relevancy to the effect on splenic cell proliferation than normal group. 13. The effect on cytokine gene expression of all the sample groups were increased than control group. 14. In flow cytometry there's no significant relation in number of $CD8^+$, $CD19^+$ cell, however, the number of $CD4^+$ cell and NK cell in sample groups were increased than in control group. Above the results showed that aqua-acupuncture of Cistanches Herba infusion solution has effects of anti-cancer, anti-metastasis and immune response improvement.

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Relationship between Intake of Milk and Milk Products and Bone Health by Sex and Age-Group in Koreans - Using Data from the Korea National Health and Nutrition Examination Survey 2008~2011 (성별, 연령별에 따른 우유·유제품 섭취와 골 건강과의 관련성 - 2008~2011 국민건강영양조사 자료를 이용하여)

  • Baek, Sang Woo;Lee, Heon Ok;Kim, Hyun Ja;Won, Eun Sook;Ha, Young Sik;Shin, Yong Kook;Om, Ae Son
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.4
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    • pp.513-522
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    • 2017
  • This study was conducted to examine the relationships between milk and milk product intake and bone health. The data from the 2008~2011 Korean National Health and Nutrition Examination Survey (KNHANES) were used for data analysis. Subjects included 4,626 men and 6,144 women aged 19 to 64 years. Daily intake frequency of milk and milk products was obtained using a food frequency questionnaire and divided into two categories: less than one serving per day and more than one serving per day. Bone mineral density (BMD) values of total femur, femoral neck, and lumbar spine were compared based on daily intake frequency, and relationships between milk and milk product daily intake frequency and osteoporosis risk were evaluated based on logistic regression. In men aged 30~39, BMDs of total femur and femoral neck were significantly higher in the group that consumed milk more than one serving per day (P<0.05). Intake frequency of milk and milk products was also significantly related to both BMDs of total femur and femoral neck. The odds ratio (OR) for milk intake frequency (more than one serving per day) compared to intake frequency less than one serving per day was 0.36 [95% confidence interval (CI) 0.21~0.62], and the OR for milk and milk products intake frequency (more than one serving per day) was 0.49 (95% CI 0.28~0.86) in women aged 50~64. These results indicate that increased consumption of milk and its products is associated with reduced risk of bone health disease, and adequate intakes of milk and milk products might play an important role in maintaining optimum bone health. Further research on the causal relationship and dose-response association between milk intake and bone heath using prospective cohort data is required prior to applying the observed results to programs that prevent bone health problems.

Influence of rutin on the effects of neonatal cigarette smoke exposure-induced exacerbated MMP-9 expression, Th17 cytokines and NF-κB/iNOS-mediated inflammatory responses in asthmatic mice model

  • Liu, Li-Li;Zhang, Yan;Zhang, Xiao-Fang;Li, Fu-Hai
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.5
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    • pp.481-491
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    • 2018
  • Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised $CD4^+CD25^+Fox3^+$ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. $NF-{\kappa}B$ and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.

Potential of Lilium lancifolium in Alleviating Pain and Inflammation in a Rat Model of Monosodium Iodoacetate-Induced Osteoarthritis

  • Kim, Jisoo;Kim, Joo Yun;Jeong, Ji-Woong;Choi, Il dong;Park, Soo-Dong;Lee, Jung Lyoul;Sim, Jae-Hun
    • Korean Journal of Plant Resources
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    • v.33 no.6
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    • pp.638-644
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    • 2020
  • Lilium lancifolium (LL) is widely cultivated in East Asia and used to attenuate airway diseases. Our current study aimed to investigate the therapeutic effect of LL on pain level and inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). We first examined the effect of LL on inflammatory cytokines and inflammatory mediators in IL-1β-treated HTB-94 cells. The LL extract was found to significantly inhibit the levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), and prostaglandin-E2 (PGE-2) in Interleukin-1 β (IL-1β)-stimulated HTB-94 cells in a dose-dependent manner. Moreover, chronic oral administration of LL effectively restored the weight-bearing distribution in the rat model of MIA-induced OA. In addition, administration of LL inhibited inflammatory cytokines and inflammatory mediators, such as C-reactive protein (CRP), IL-6, leukotriene B4 (LTB-4), PGE-2, and matrix metalloproteinase-9 (MMP-9). Our findings collectively suggested LL as one of the potential therapeutic agents for OA, owing to its properties of reducing pain and inflammatory responses.

Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis

  • Rui Chen;Mengting Wang;Qiaoling Qi;Yanli Tang;Zhenzhao Guo;Shuai Wu;Qiyan Li
    • Journal of Periodontal and Implant Science
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    • v.53 no.1
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    • pp.20-37
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    • 2023
  • Purpose: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. Methods: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. Results: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant antiinflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. Conclusions: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

Apoptotic Effect of co-treatment with HS-1200 and Cisplatin on SCC25 Human Tongue Squamous Cell Carcinoma Cell Line (HS-1200과 cisplatin의 병용처리가 사람구강암세포에 미치는 세포자멸사 효과에 대한 연구)

  • Kim, Duk-Han;Kim, In-Ryoung;Park, Bong-Soo;Ahn, Yong-Woo;Jeong, Sung-Hee
    • Journal of Oral Medicine and Pain
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    • v.38 no.3
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    • pp.221-233
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    • 2013
  • Bile acids are polar derivatives of cholesterol essential for the absorption of dietary lipids and regulate the transcription of genes that control cholesterol homeostasis. Recently it have been identified the synthetic chenodeoxycholic acid (CDCA) derivatives HS-1200 and cisplatin showed apoptisis-inducing activity on various cancer cells in vivo and in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with HS-1200 and cisplatin on human tongue squamous cell carcinoma cells (SCC25 cells). To investigate whether the co-treatment with HS-1200 and cisplatin compared to each single treatment efficiently reduces the viability of SCC25 cells, MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis DNA hypoploidy. Westen blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) change were also assayed. In this study, co-treatment with HS-1200 and cisplatin on SCC25 cells showed several lines of apoptotic manifestation such as nuclear condensations, DNA fragmentation, reduction of MMP and proteasome activity, the increase of Bax and the decrease of Bcl-2, decrease of DNA content, the release of cytochrome c into cytosol, translocation of AIF and DFF40 (CAD) onto nuclei, and activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD) whereas each single treated SCC25 cells did not show these patterns. Although the single treatment of $25{\mu}M$ HS-1200 and $4{\mu}g/ml$ cisplatin for 24 h did not induce apoptosis, the co-treatment of these reagents prominently induced apoptosis. Therefore our data provide the possibility that the combination therapy with HS-1200 and cisplatin could be considered as a novel therapeutic strategy for human squamous cell carcinoma.

The Effects of Taklisodok-eum Extract on Acute Sinusitis-induced mouse (탁리소독음(托裏消毒飮)이 급성 부비동염을 유발시킨 마우스에 미치는 영향)

  • Lee, Sang-Moon;Hong, Seung-Ug
    • The Journal of Korean Medicine
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    • v.29 no.4
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    • pp.1-12
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    • 2008
  • Background and Objectives: Sinusitis is a common disease in the otorhinolaryngology field. It is inflammatory change of the mucous membrane which surrounds the sinus. The aim of this study was to investigate the anti-inflammatory effects of the Taklisodok-eum (TSE) extract on the mouse model with acute sinusitis induced by S. pneumoniae. Methods: Thirty six-week-old male BALB/c mice were divided into three groups: the normal group, the group inoculated with S. pneumoniae which caused allergic rhinitis (control group), and the group treated with the TSE extract after it was treated the same as the control group (sample group). Results: $NF-{\kappa}B$ activation was suppressed, and iNOS & COX-2 production were inhibited by TSE in acute sinusitis. Apoptosis was increased by TSE in acute sinusitis. The number of eosinophils in the sample group noticeably decreased when compared to the control group. In the general morphologic change, the increase of damaged respiratory ciliated epithelia & eosinophils' infiltration was lessin the sample group. Goblet cells were maintained in the sample group. MMP-9, HSP-70 and BrdU decreased in the sample group. Apocrine secretion decreased in the sample group. Conclusion: The findings in this study show that TSE reduces acute sinusitis through its anti-inflammatory effects, such as the inhibition of $NF-{\kappa}B$ activity.

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Study on Antitumor Activity of Hongsamdaibotang(HDT-C) (홍삼대보탕(紅蔘大補湯)의 항암활성(抗癌活性) 및 항전이(抗轉移) 효과(效果)에 관(關)한 연구(硏究))

  • Kim, Sung-Hoon;Choi, Byong-gyun;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.9 no.1
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    • pp.143-153
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    • 2000
  • To evaluate the antitumor activity and antimetastatic effects of Hongsam -daibotang(HDT-C), studies were done experimentally. The results were obtained as follows: 1. In cytotoxicity against A549, SK-OV-3 and B16-BL6 concentration inhibi ting cell growth up to below 30% of control was recognized at $10^{-3}g/ml$ of HDT-C. 2. The T/C% was 145.4% in HDT-C treated group in S-180 bearing ICR mice. 3. In Inhibitory effect on activity of DNA topoisomerase I, the $IC_{50}$ was shown $100-200{\mu}g/ml$ of HDT-C. 4. The expressing $TNF-{\alpha}$ was increased in HDT-C treated group as compared with control. 5. The expressing MMP-9 was decreased in HDT-C treated group as compared with control. 6. HDT-C extracts exhibited efficient adhesive effect of A549, B16-BL6 cell to complex extracellular matrix. 7. In CAM assays, angiogenesis was significantly inhibited in HDT-C treated group than control group. 8. In pumonary colonization assay, a number of colonies in the lungs were decreased significantly in HDT-C treated group as compared with control group. 9. In hematological changes in B16-BL6 injected C57BL/6, numbers of WBC and were decreased insignificantly and also those of platelet were increased insignificantly in HDT-C treated group as compared with control. 10. In the histological changes of lung in B16-BL6 injected mice, infiltration of cancer cells were inhibited effectively in HDT-C treated groups whereas many cancer cells were infiltrated into erivascular and peribronchiol of control group. These results suggested that HDT-C extracts might be usefully applied for prevention and treatment of cancer.

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Influence of Herb-combined Remedies Based on "Yooam" Prescription of Dongeuibogam on Migration and Invasion of B16F10 Melanoma Cells (B16F10 흑색종 세포의 이동과 침윤에 미치는 동의보감 "유암" 처방에 근거한 한약복합처방들의 영향)

  • Choi, Eun Ok;Kwon, Da Hye;Hwang-Bo, Hyun;Kim, Min Young;Ji, Seon Yeong;Hong, Su Hyun;Park, Cheol;Hwang, Hye-Jin;Choi, Yung Hyun
    • Herbal Formula Science
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    • v.26 no.3
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    • pp.223-236
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    • 2018
  • Objectives : We compared the inhibitory effects of herb-combined remedies, which were recorded on "Yooam" prescription of Dongeuibogam, on cell migration and invasion, two critical cellular processes that are often deregulated during metastasis, in B16F10 melanoma cells. For this purpose, water extracts of Sipyukmiryukieum (SYMRKU), Danjacheongpitang (DJCPT), Cheongganhaeultang (CGHUT) and Jipaesan (JPS) were used. Methods : Cytotoxicity was assessed by an MTT assay. Wound healing and matrigel transwell assays were used to examine on B16F10 cell migration and invasion. The levels of mRNA and protein expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) were analyzed by RT-PCR and Western blotting. Results : Our data showed that DJCPT showed the strongest inhibitory effect among the four prescriptions in inhibiting cell motility of B16F10 melanoma cells within the concentration range that was not cytotoxic. The inhibitory potential of colony formation was higher in DJCPT and SYMRKU compared to the other two types of prescriptions, and the inhibitory effect of invasiveness is shown in order of DJCPT, SYMRKU, CGHUT and JPS. DJCPT, and SYMRKU strongly inhibited the activity and expression of MMP-2 and MMP-9, which are important mediators in cancer invasion, compared to CGHUT and JPS, and the increased expression of TIMP-1 and TIMP-2 was also more effective in these two prescriptions. In conclusion, DJCPT is expected to exhibit the most potent blocking effect on migration and invasion among four herb-combined remedies compared in B16F10 melanoma cells. Conclusion : Overall, the results of this study will be used as an important source to validate these prescriptions in animal models and to understand the mechanism of action of herbal remedies recorded in Dongeuibogam.

Expression and Function of Calcineurin in Inflammatory Arthritis (류마티스 관절염에서 칼시뉴린의 발현과 기능)

  • Park, Bo-Hyoung;Yoo, Seung-Ah;Hong, Kyung-Hee;Hyoung, Bok-Jin;Hwang, Yu-Na;Cho, Chul-Soo;Park, Won;Kim, Wan-Uk
    • IMMUNE NETWORK
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    • v.6 no.1
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    • pp.33-42
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    • 2006
  • Background: Calcineurin plays a crucial role in T cell activation, cell growth, apoptosis, and angiogenesis, and its over-expression has been implicated in the pathogenesis of cardiomyopathy and stroke. However, the expression and function of calcineurin in the pathologic lesion of chronic inflammatory diseases, like rheumatoid synovium, remain to be defined. This study was aimed to determine the role of calcineurin in inflammatory arthritis and investigate the expression and function of calcineurin in the rheumatoid synovium and synoviocytes, the actual site of chronic inflammation. Methods: Immuno-histochemical staining using specific antibody to calcineurin was perfomed in the synovium of rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) from RA and osteoarthritis (OA) patients were isolated from RA and OA patients, and cultured with IL-1${\beta}$ and TNF-${\alpha}$ in the presence or absence of cyclosporin A, a calcineurin inhibitor. The calcineurin expression was assessed by phosphatase assay and Western blotting analysis. IL-6, -10, -17, matrix metalloproteinase (MMP)-1, -2, -3, and -9 released into the culture supernatants were measured by ELISA. After transfection with GFP-Cabin 1 gene into synoviocytes, the levels of IL-6 and MMPs were measured by ELISA. Results: Calcineurin was highly expressed in the lining layer of synovium and cultured synoviocytes of RA patients. The elevated calcineurin activity in the rheumatoid synoviocytes was triggered by proin flammatory cytokines such as IL-1${\beta}$ and TNF-${\alpha}$. In contrast, IL-10, an anti-inflammatory cytokine, failed to increase the calcineurin activity. The targeted inhibition of calcineurin by the over-expression of Cabin 1, a natural calcineurin antagonist, inhibited the production of IL-6 and MMP-2 by rheumatoid synoviocytes in a similar manner to the calcineurin inhibitor, cyclosporin A. Conclusion: These data suggest that abnormal activation of calcineurin in the synoviocytes may contribute to the pathogenesis of chronic arthritis, and thus provide a potential target for controlling inflammatory arthritis.