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류마티스 관절염 환자의 말초혈액 단핵세포에서 Phosphoinositide 3-Kinase (PI3K)/Akt와 Nuclear Factor KappaB (NF-κB) 신호전달을 통한 IL-17 생성조절 (Regulation of Interleukin-17 Production in Patients with Rheumatoid Arthritis by Phosphoinositide 3-kinase (PI3K)/Akt and Nuclear Factor KappaB (NF-κB) Dependent Signal Transduction Pathway)

  • 김경운;조미라;이상헌;민소연;박미경;박성환;주대명;김호연
    • IMMUNE NETWORK
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    • 제3권4호
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    • pp.310-319
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    • 2003
  • Inflammatory mediators has been recognized as an important role in the pathogenesis of rheumatoid arthritis (RA). IL-17 is increasingly recognized as an important regulator of immune and inflammatory responses, including induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence of the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. However, the signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in the regulation of IL-17 production in RA. PBMC were separated from RA (n=24) patients, and stimulated with various agents (anti CD3, anti CD28, PHA, ConA, IL-15). IL-17 levels were determined by sandwich ELISA and RT-PCR. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody, PHA, IL-15 or MCP-1 (P<0.05). ConA also strongly induced IL-17 production (P<0.001), whereas TNF-alpha, IL-1beta, IL-18 or TGF-beta did not. IL-17 was detected in the PBMC of patients with osteoarthritis (OA) but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K-Akt pathway and activation of the PI3K-Akt pathway resulted in a pronounced augmentation of nuclear factor kappaB ($NF-{\kappa}B$). IL-17 production by activated PBMC in RA is completely or partially blocked in the presence of $NF-{\kappa}B$ inhibitor PDTC and PI3K-Akt inhibitor, wortmannin and LY294002, respectively. Whereas the inhibition of AP-1 and extracellular signal-regulated kinase (ERK)1/2 did not affect IL-17 production. These results provide new insight into that PI3K/Akt and $NF-{\kappa}B$ dependent signal transduction pathway could be involved in the overproduction of key inflammatory cytokine, IL-17 in rheumatoid arthritis.

Comparison of Inhibitory Effect of 17-DMAG Nanoparticles and Free 17-DMAG in HSP90 Gene Expression in Lung Cancer

  • Mellatyar, Hassan;Akbarzadeh, Abolfazl;Rahmati, Mohammad;Ghalhar, Masoud Gandomkar;Etemadi, Ali;Nejati-Koshki, Kazem;Zarghami, Nosratallah;Barkhordari, Amin
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권20호
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    • pp.8693-8698
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    • 2014
  • Background: Up-regulation of hsp90 gene expression occurs in numerous cancers such as lung cancer. D,L-lactic-co-glycolic acid-poly ethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG may inhibit the expression. The purpose of this study was to examine whether nanocapsulating 17DMAG improves the anti cancer effect over free 17DMAG in the A549 lung cancer cell line. Materials and Methods: Cells were grown in RPMI 1640 supplemented with 10% FBS. Capsulation of 17DMAG is conducted through double emulsion, then the amount of loaded drug was calculated. Other properties of this copolymer were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity on the grown of lung cancer cell line was carried out through MTT assay. After treatment, RNA was extracted and cDNA was synthesized. In order to assess the amount of hsp90 gene expression, real-time PCR was performed. Results: In regard to the amount of the drug load, IC50 was significant decreased in nanocapsulated(NC) 17DMAG in comparison with free 17DMAG. This was confirmed through decrease of HSP90 gene expression by real-time PCR. Conclusions: The results demonstrated that PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of hsp90 expression by enhancing uptake by cells. Therefore, PLGA-PEG could be a superior carrier for this kind of hydrophobic agent.

Elevated Serum IL-17A but not IL-6 in Glioma Versus Meningioma and Schwannoma

  • Doroudchi, Mehrnoosh;Pishe, Zahra Ghanaat;Malekzadeh, Mahyar;Golmoghaddam, Hossein;Taghipour, Mousa;Ghaderi, Abbas
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권9호
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    • pp.5225-5230
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    • 2013
  • Background: There is a Th1/Th2 cytokine imbalance and expression of IL-17 in patients with brain tumours. We aimed to compare the levels of IL-17A and IL-6 in sera of glioma, meningioma and schwannoma patients as well as in healthy individuals. Materials and Methods: IL-17A and IL-6 levels were measured in sera of 38 glioma, 24 meningioma and 18 schwannoma patients for comparison with 26 healthy controls by commercial ELISA assays. Results: We observed an increase in the IL-17A in 30% of glioma patients while only 4% and 5.5% of meningioma and schwannoma patients and none of the healthy controls showed elevated IL-17A in their sera ($0.29{\pm}0.54$, $0.03{\pm}0.15$ and $0.16{\pm}0.68$ vs. $0.00{\pm}0.00pg/ml$; p=0.01, p=0.01 and p=0.001, respectively). There was also a significant decrease in the level of IL-6 in glioma patients compared to healthy controls ($2.34{\pm}4.35$ vs. $4.67{\pm}4.32pg/ml$; p=0.01). There was a direct correlation between the level of IL-17A and age in glioma patients (p=0.005). Glioma patients over 30 years of age had higher IL-17A and lower IL-6 in their sera compared to the young patients. In addition, a non-significant grade-specific inverse trend between IL-17A and IL-6 was observed in glioma patients, where high-grade gliomas had higher IL-17A and lower IL-6. Conclusions: Our data suggest a Th17 mediated inflammatory response in the pathogenesis of glioma. Moreover, tuning of IL-6 and IL-17A inflammatory cytokines occurs during progression of glioma. IL-17A may be a potential biomarker and/or immunotherapeutic target in glioma cases.

인간 암세포인 AGS와 T24에서의 apoptosis 유도에 미치는 Bacillus subtilis 혈전용해효소 BK-17의 영향 (Effect of a Fibrinolytic Enzyme (BK-17) from Bacillus subtilis on Apoptosis Induction in AGS and T24 Human Carcinoma Cells)

  • 백현;서민정;김민정;이혜현;강병원;박정욱;최영현;서권일;정영기
    • 생명과학회지
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    • 제23권10호
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    • pp.1252-1259
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    • 2013
  • 인간 암세포의 생육에 미치는 혈전용해효소(BK-1)의 영향을 조사하기 위해, 세포증식, 생존력, 형태변화 및 apoptosis 유도 등을 포함한 여러 가지 생화학적 실험을 하였다. 그 결과, AGS 인간 위장 암세포 및 T24 인간 방광 암세포상에의 BK-17 처리는 그 암세포들의 생존력 및 생율을 농도의존적 방법으로 감소시켰다. 현미경 관찰은, BK-17 처리에 의한 항 생육 효과는 막 수축, 세포의 rounding up, apoptotic bodies와 같은 형태학적 변화를 나타내었다. 특히, RT-PCR과 Western blotting data는, BK-17 처리가 항 apoptosis Bcl-2 군들 특히 Bcl-2, and $Bcl-X_L$의 down-regulation 그리고 AGS 세포에서, apoptosis 촉진 매개체 Bax와 Bad의 up-regulation를 유도했다는 것을 보여주었다. BK-17에 의해 유도된 AGS 세포의 apoptosis는 caspase-3, caspase-8 그리고 caspase-9의 단백질가수분해 활성과 관련이 있었다. 이상의 결과를 볼 때, BK-17은 apoptotic cell death의 유도와 밀접한 관련이 있다는 것을 보여주고 있다.

닭에서의 지방산(脂肪酸) 생합성(生合成)에 미치는 급여지방산(給與脂肪酸)의 영향(影響) (Fatty Acid Biosynthesis of Chicken Fed Various Long Chain Fatty Acids)

  • 고태송
    • 한국식품과학회지
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    • 제10권3호
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    • pp.313-319
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    • 1978
  • 무지방사료(無脂肪飼料) 및 여기에 17:0, 18:0 혹은 18:2을 첨가(添加)한 사료(飼料)를 병아리에 급여(給與)해서 간장(肝臟) 및 혈장(血漿)의 각지질분획(各脂質分劃)의 지방산조성(脂肪酸組成)에 미치는 급여지방산(給與脂肪酸)의 영향(影響)을 조사(調査)하였다. 그 결과(結果) 간장중(肝臟中)의 총지질함량(總脂質含量) 및 각지질분획(各脂質分劃)의 함량(含量)은 급여지방산(給與脂肪酸)에 의해서 영향(影響)받지 않았다. 그러나 17:0을 급여(給與)하면 간장(肝臟) 및 혈장(血漿)의 각지질분획(各脂質分劃)에 17:0 및 17:1 출현(出現)하고, 혈장(血漿)트리그리세라이드에서는 17:0이 또한 혈장(血漿)콜레스테롤에스텔에서는 17:1이 다른 분획(分劃)보다도 유의(有意)하게 높았다. 더욱이 간장(肝臟)에서는 각분획(各分劃)사이에 양지방산(兩脂肪酸)의 분포치(分布値)에 큰 차이(差異)가 없었다. 18:2의 급여(給與)도 17:0을 급여(給與)한때와 같이 간장(肝臟) 및 혈장(血漿)의 각지질분획(各脂質分劃)에 18:2이 출현(出現)하고, 특(特)히 간장인지질분획(肝臟燐脂質分劃)에서 18:2의 분포치(分布値)는 다른분획(分劃)보다도 유의(有意)하게 높았다. 그러나 18:0을 급여(給與)해도 이것이 간장(肝臟) 및 혈장중(血漿中)에 특별적(特別的)으로 증가(增加)하지는 않았다. 또한 17:0 및 18:2과 같은 외인성지방산(外因性脂肪酸)의 급여(給與)에 의하여 내인적(內因的)으로 합성(合成)되는 16:1 및 18:1의 분포치(分布値)는 간장(肝臟)에서 감소(減少)하는 경향(傾向)을 나타내었다.

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재조합 대장균 pYC17이 생성하는 세포내 invertase의 생합성 조절 (Biosynthetic Regulation of Invertase from Recombinant E. coil pYC17)

  • 이성훈;노재덕;이대형;이종수
    • 자연과학논문집
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    • 제17권1호
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    • pp.103-111
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    • 2006
  • 호알칼리성이며 고온성인 Bacillus sp. TA-11이 세포내로 생성하는 invertase 유전자를 대장균에 클로닝 시켜 얻은 재조합 E. coil pYC17의 invertase 생합성 조절양상을 조사 하였다. 재조합 E. coil의 invertase는 30 mM sucrose에 의해 3시간에 가장 효과적으로 유도 되었으며 조합 E. coil pYC17의 sucrose에 의한 invertase 유도는 10 mM의 glucose 농도에서 심하게 억제 되었다. 이러한 재조합 E. coil pYC17에서의 invertase 생합성 조절 양상은 친주인 Bacillus sp. TA-11과 유사하였으나 저해농도는 낮았다.

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IL-17A Levels in the Sera of Patients with Gastric Cancer Show Limited Elevation

  • Malek-Hosseini, Zahra;Taherinejad, Marziye;Malekzadeh, Mahyar;Ghaderi, Abbas;Doroudchi, Mehrnoosh
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권16호
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    • pp.7149-7153
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    • 2015
  • Background: Inflammation plays a major role in the development and progression of gastric and other gastrointestinal tumors. The IL-17 family of cytokines has been under investigation as targets of immunotherapy. Materials and Methods: We investigated the levels of IL-17A inflammatory cytokine in the sera of 57 patients with gastric cancer (GC) and 90 healthy age/sex matched controls using ELISA methods. Results: In only 5 (8.8%) of the patients' sera was IL-17A detectable. No IL-17A was apparent in the sera of healthy controls. The maximum concentration of IL-17A in patients was 7.004 pg/ml. Vascular and lymphatic invasions were only seen in one of the 5 positive cases. Although all of them were in the age group >60 years, no correlation was seen between age and IL-17A level. These results are somewhat different from our findings for colorectal cancer (CRC) in the same population. Conclusions: It is possible that the inflammopathology of CRC and GC are rather different, at least in Fars, a southern province of Iran.

Th17 responses and host defense against microorganisms: an overview

  • Van De Veerdonk, Frank L.;Gresnigt, Mark S.;Kullberg, Bart Jan;Van Der Meer, Jos W.M.;Joosten, Leo A.B.;Netea, Mihai G.
    • BMB Reports
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    • 제42권12호
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    • pp.776-787
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    • 2009
  • T helper (Th) 17 cells have recently been described as a third subset of T helper cells, and have provided new insights into the mechanisms that are important in the development of autoimmune diseases and the immune responses that are essential for effective antimicrobial host defense. Both protective and harmful effects of Th17 responses during infection have been described. In general, Th17 responses are critical for mucosal and epithelial host defense against extracellular bacteria and fungi. However, recent studies have reported that Th17 responses can also contribute to viral persistence and chronic inflammation associated with parasitic infection. It has become evident that the type of microorganisms and the setting in which they trigger the Th17 response determines the outcome of the delicate balancethat exists between Th17 induced protection and immunopathogenesis.

Study on the Formation and the Magnetic Properties of $Sm_2Fe_{17}N_x$-type Interstitial Material

  • Kwon, H.W.
    • Journal of Magnetics
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    • 제1권1호
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    • pp.19-23
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    • 1996
  • In the present study, the $Sm_2Fe_{17}N_x$-type interstitial materials have been prepared by reaction between Nb-free or Nb-containing $Sm_2Fe_{17}$-type alloy and $N_2$ gas. Nitrogenation behaviour of the $Sm_2Fe_{17}N_x$-type material and disproportionation characteristics of the nitrogenated materials have been studied by means of differential thermal analysis (DTA) and thermopiezic analysis (TPA). Magnetic properties of the produced $Sm_2Fe_{17}N_x$-type interstitial materials were characterised in vibrating sample magnetometer (VSM) or thermomagnetic analyser (TMA). Epoxy-bonded or Zn-bonded $Sm_2Fe_{17}N_x$-type magnets were prepared, and their magnetic properties were investigated. It has been found that nitrogenation kinetics of the Sm2Fe17Nx-type alloy is improved significantly by the Nb-substitution for Fe in the alloy. The Nb-substitution is also found to enhance thermal stability of the $Sm_2Fe_{17}N_x$-type interstitial material. Hard magnetic properties of the interstitial materials produced from Nb-free orNb-containing alloy is high enough (intrinsic coercivity : over 7 kOe) for application as bonded permanent magnets. The good hard magnetic properties of the interstitial material are maintained in the epoxy-bonded magnet. Intrinsic coercivity of the Zn-bonded magnets is improved significantly as post-bonding annealing time increases.

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