Glucocorticoid-induced tumor necrosis factor receptor–related protein co-stimulation facilitates tumor regression by inducing IL-9–producing helper T cells

Kim, Il-Kyu,Kim, Byung-Seok,Koh, Choong-Hyun,Seok, Jae-Won,Park, Jun-Seok,Shin, Kwang-Soo,Bae, Eun-Ah,Lee, Ga-Eun,Jeon, Hyewon,Cho, Jaebeom,Jung, Yujin,Han, Daehee,Kwon, Byoung S,Lee, Ho-Young,Chung, Nature Publishing Group, a division of Macmillan P 2015 Nature medicine Vol.21 No.9

<P>T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (T(H)9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-kappa B-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting T(H)9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies.</P>

세신약침(細辛藥鍼)의 천식억제 및 면역조절효과에 대한 실험적 연구

김일구 ( Il Gu Kim ),김영일 ( Young Il Kim ),홍권의 ( Kwon Eui Hong ),임윤경 ( Yun Kyoung Yim ),이현,이병렬 ( Byung Ryul Lee ) 대한경락경혈학회 2004 Korean Journal of Acupuncture Vol.21 No.1

Objectives and methods: The aim of this study was to investigate the effect of AHCR(ASARI HERBA CUM RADICE) herbal acupuncture at St36 on ovalbumin-induced asthma in mice. C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). Two experimental groups were treated with different concentrations(1%, 0.1%) of AHCR-HAS at Chok-samni (St36) for the later 8 weeks (3times/week). Results: 1. Lung weight of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 2. Total Leukocytes in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with that of control group. 4. The number of Gr-1+ /CD11b+, CCR3+, CD4+, CD3e+/CD69+, IgE+/B220+ cells in the lungs of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 5. The number of CD8+ cells in the lungs of the mice group treated with AHCR-HA didn`t show significant difference compared with that of control group. 6. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with AHCR-HA decreased significantly compared with that of control group. Conclusion: We conclude that AHCR-HA is effective on OVA-induced asthma in C57BL/6 mouse.

방풍의 항염 효과 기전

노성일 ( Sung Il Noh ),김상돈 ( Sang Don Kim ),박성철 ( Sung Cheul Park ),서병윤 ( Byung Yun Seo ),염승룡 ( Seung Ryong Yeom ),권영달 ( Young Dal Kwon ),신병철 ( Byung Cheul Shin ),송용선 ( Yung Sun Song ) 한방재활의학과학회 2005 한방재활의학과학회지 Vol.15 No.2

목적 : 방풍은 임상적으로 관절염을 포함한 다양한 염증성 질환 치료제로 사용되어 왔다. 본 연구에서는 인간 비만세포를 이용하여 세포 독성에 영향을 주지 않는 농도에서 방풍의 항염 효과 및 그 기전을 검토했다. 방법 : 인간의 HMC-1세포를 IMDM에서 페니실린, 스트렙토마이신, 모노티오글리세린를 첨가하여 배양하고 방풍추출액을 투여하였다. 그 다음 MTT, ELISA, RT-PCR, 세포내 칼슘측정, 핵단백분석을 이용하여 TNF-α, IL-6, IL-8 각각의 형성과 mRNA발현, 세포내 칼슘 수준, NF-κB 발현에 대한 방풍추출액의 반응을 측정하고 통계처리 하였다. 결과 : 방풍은 PMA와 calcium ionophore A23187로 활성화된 비만세포에서 세포내 칼슘 수준과 NF-κB, TNF-α와 IL-6의 발현을 억제 시켰고 RT-PCR을 이용한 mRNA 발현에서 TNF-α와 IL-6의 발현을 억제하였다. 결론 : 방풍은 비만세포내 칼슘 수준 및 NF-κB의 활성을 억제하고 염증성 세포 활성 물질인 TNF-α와 IL-6의 분비도 억제하여 항염 효과를 나타냄을 암시하고 있다.

상엽약침(桑葉藥鍼)의 천식억제효과(喘息抑制效果)에 대한 실험적 연구

신성찬 ( Sung Chan Shin ),김영일 ( Young Il Kim ),홍권의 ( Kwon Eui Hong ),임윤경 ( Yun Kyoung Yim ),이현 ( Hyun Lee ),이병렬 ( Byung Ryul Lee ) 대한경락경혈학회 2004 Korean Journal of Acupuncture Vol.21 No.3

Objective: The aim of this study was to investigate the effect of Mori Folium herbal acupuncture at St36 on ovalbumin-induced asthma hi mice. Methods: C57BL/6 mice were sensitized and challenged with OVA (ovalbumin) for 12 weeks (once a week) Two experimental groups were treated with different concentrations (1%, 0.1%) of Mori Folium herbal acupuncture at Chok-samni (St36) for the later 8 weeks (3times/week). Result: 1. Lung weight of the mice group treated with Mori Folium herbal acupuncture decreased significantly compared with that of control group. 2. Total Leukocytes in BALE of the mice soup treated with Mori Folium herbal acupuncture decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated with Mori Folium herbal acupuncture decreased significant1y compared with that of control group. 4. The number of Gr-1+/CD11b, CCR3+, CD4+, CD8+, CD3e+/CD69+, IgE+/B220+ cells in the lung of the mice group treated with Mon Folium herbal acupuncture deceased significantly compared with that of group. 5. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with Mori Folium herbal acupuncture deceased significantly compared with that of control group. 6. The concentration of IL-4 in BALF of the mice group treated with Mori Folium herbal acupuncture decreased signifint1y compared with that of control group. Conclusion: We conclude that Mori Folium herbal acupuncture is effective on OVA-induced asthma of C57BL/6 mouse.

세신약침(細辛藥鍼)의 천식억제 및 면역조절효과에 대한 실험적 연구

김일구,김영일,홍권의,이현,이병렬,임윤경,Kim, Il-Gu,Kim, Young-Il,Hong, Kwon-Eui,Lee, Hyeon,Lee, Byung-Ryul,Yim, Yun-Kyoung 경락경혈학회 2004 대한침구의학회지 Vol.21 No.1

Objectives and methods : The aim of this study was to investigate the effect of AHCR(ASARI HERBA CUM RADICE) herbal acupuncture at St36 on ovalbumin-induced asthma in mice. C57BL/6 mice were sensitized and challenged with OVA(ovalbumin) for 12 weeks(once a week). Two experimental groups were treated with different concentrations(1%, 0.1%) of AHCR-HAS at Chok-samni (St36) for the later 8 weeks (3times/week). Results 1. Lung weight of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 2. Total Leukocytes in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with those of control group. 3. The number of Eosinophils in BALF of the mice group treated wtih AHCR-HA decreased significantly compared with that of control group. 4. The number of $Gr-1^+/CD11b^+,\;CCR3^+,\;CD4^+,\;CD3e^+/CD69^+,\;IgE^+/B220^+$ cells in the lungs of the mice group treated with AHCR-HA decreased significantly compared with that of control group. 5. The number of $CD8^+$ cells in the lungs of the mice group treated with AHCR-HA didn't show significant difference compared with that of control group. 6. The concentration of IgE, IL-13, IL-4 in serum of the mice group treated with AHCR-HA decreased significantly compared with that of control group. Conclusion We conclude that AHCR-HA is effective on OVA-induced asthma in C57BL/6 mouse.

혈소판 응집 억제제의 효과 측정법에 대한 고찰과 지원자에서 Triflusal의 혈소판 응집 억제능 평가

이병요,장힘찬,백인환,윤휘열,권광일 충남대학교 약학대학 의약품개발연구소 2010 藥學論文集 Vol.25 No.-

The anti-platelet agent is a member of a class of pharmaceuticals that decreases platelet aggregation and inhibits thrombus formation. They are effective in the arterial circulation and widely used in primary and secondary prevention of thrombotic cerebrovascular or cardiovascular disease. As a method for estimating the effects of anti-platelet agent, platelet aggregation was conventionally measured using the optical method or the impedance method. Several alternate methods currently in development or recently developed were considered, including luminescence method, flow cytometry, laser-light scattering method, and Verify Now-P2Y12 assay. Principles, advantages, and disadvantages of the optical method, impedance method, and the other alternate platelet aggregation methods were discussed in this report. 15 human volunteers were recruited for the evaluation of the efficacy of triflusal using the optical method. After the oral administration of a single dose of 900mg, 15 subjects received eight doses administered at 24-hour intervals of 600mg triflusal. Using platelet rich-plasma from above subjects, we performed baseline platelet aggregation test induced by adenosine diphosphate(ADP), collagen, and arachidonic acid. The results of platelet aggregation test after triflusal administration were compared with the baseline study. Triflusal significantly inhibited platelet aggregation induced by ADP (33.0±21.3%) and arachidonic acid (99.1±1.2%), respectively. Therefore, we concluded that anti-platelet aggregation effect of triflusal can be studied successfully with the optical method. Each of the platelet aggregation methods has value for evaluating the effects by various mechanisms of the anti-platelet agents. The ideal method for estimating the platelet aggregation as it relates to safety and efficacy in patients treated with anti-platelet agents will need to be determined in clinical trials.

마리화나 흡연 후 발생한 뇌경색

이일형,김성민,배재천,권기한,이병철 대한신경과학회 1999 대한신경과학회지 Vol.17 No.2

Mokpo-MS를 利用한 F_1用種子 採種方法과 採種能力

權炳善,文溶植,李鍾一 조선대학교 농업연구소 1982 農業硏究 Vol.1982 No.1

成分改良된 Mokpo-MS를 利用하여 F_l用種子 採種方法과 採種能力을 究明코자 實驗한바 MS와 花粉親間 의 交互栽植時에 10a 當 F_l採種量은 어느 組合에서나 다 같이 MS 1 畦, 花粉親 1畦 交互畦栽植에서118~127kg의 F_l採種量을 얻었고 MS 2 畦, 花粉親 1 畦 交互畦 栽植에서는 101~ 118Kg, MS 3 畦, 花粉親 1 畦 交互畦 栽植에서는 86~89Kg의 F_l採種量을 얻었다. The F_1 seed production in per l0a has been produced by 118kg to 120kg with the one row planting of pollen parents and one row alternate planting of Mokpo-MS. The other hand, two rows planting of Mokpo-MS and one row alternate planting of pollen parents has been to produced by 101kg to 118kg and three rows planting of Mokpo-MS and one row alter nate planting of pollen parents has been produced by 86 to kg in F-l seed production.

황련해독탕 및 귀비탕의 발효 전후 혈소판 응집 억제 효과에 대한 비교 연구

송병정,이수진,권광일 충남대학교 약학대학 의약품개발연구소 2012 藥學論文集 Vol.27 No.-

Recently interest of fermented oriental medicines is increasing for the purpose of disease prevention. Hwangryunghaedok-tang (HR) and Guibi-tang (GB) are widely used oriental medicines in Korea. HR and GB are well known for anti-inflammatory and anti-stress effect. Glycosides in herbal medicines are transformed to aglycone via fermentation. The fermented medicines are absorbed more and have less individual variation. In this study, HR and GB were compared before and after fermentation by anti-platelet aggregation effect. HR and GB were fermented by various lactobacillus species. The anti-platelet aggregation effect of HR and GB were measured using aggregometer by optical method. Collagen (4 μg/mL) was used as a inducer of platelet aggregation. After measuring anti-platelet aggregation effect, we analysed the data using WinnonlinⓇ program to fit simple Emax model. Then Emax and EC50 values were estimated. In results, GB had little antiplatelet effects. Emax of 5 GB samples (127, 164, 402, 442, 3163) were estimated near zero and others (129, 144, 166, 693, 744) had high EC50 values (> 1500 μg/mL). In contrast with GB, HR had antiplatelet effects. HR which was fermented by Lactobacillus casei and Lactobacillus plantarum (HR-127,HR-144) were most effective sample. Emax and EC50 of HR-127 and HR-144 was 99.99%, 174.73 μg/mL and 100.00% 160.48 μg/mL, respectively. These results indicated that Guibi-tang was inappropriate as anti-platelet aggregation agent and Hwangryunhaedok-tang would be more effective after fermentation as anti-platelet aggregation agent, warranting further study.

국내외 현황 파악을 통한 국내 소아용 의약품의 안전성.유효성 평가제도 개선 방안

이병요,이수진,권광일 충남대학교 약학대학 의약품개발연구소 2013 藥學論文集 Vol.28 No.-

Recently it has been noticed that pharmacokinetics / Pharmacodynamic (PK/PD) properties of drug in the pediatric population are different from those in adults. Clinical trials that considering age-specific properties and characteristics should be performed and safety and efficacy are established based on the clinical trials. FDA and EMEAs exists in developed countries especially America and Europe due to which there are proper guidelines for pediatric patients. However, in Korea, there doesn’t exist any guidelines and the study is focused regarding it. This study aimed to analyze the current state of safety and efficacy assessment of pediatric drug by foreingn drug regulatory agencies and suggest the regulatory methods for Korea based on FDA and EMEA guidelines and regulatory. MEDLINE and foreign drug regulatory agency database were extensively searched to obtain scientific research articles, guidance, regulations and pediatric drug review reports on foreign pediatric drug evaluation system.