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>

A novel role for bone-derived cells in ankylosing spondylitis: Focus on IL-23

Jo, Sungsin,Koo, Bon San,Lee, Bitnara,Kwon, Eunji,Lee, Young Lim,Chung, Heekyoung,Sung, Il-Hoon,Park, Ye-Soo,Kim, Tae-Hwan Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>The main aim of this study are to explore the role of bone-derived cells (BdCs) in ankylosing spondylitis (AS) and determine the underlying molecular mechanisms of IL-23 production. Primary BdCs were isolated from diced bone of facet joints obtained during surgery from seven AS patients and seven disease control (Ct) patients. Osteoblastic activity of BdCs was assessed by measuring their alkaline phosphatase activity and by alizarin red staining. Osteoblast and endoplasmic reticulum (ER) stress-related genes were assessed by quantitative PCR, immunoblotting, immunofluorescence, and immunohistochemistry. In addition, expression of IL-23 in response to BIX (selective BIP inducer X)-induced ER stress was evaluated by qPCR and ELISA. Protein interaction and binding to IL-23 promoter were confirmed by Immunoprecipitation and Chromatin immunoprecipitation, respectively. Transcript levels of genes involved in osteoblast function, as well as of the ER stress marker were higher in the AS group than the Ct group, and elevated RUNX2, BiP and IL-23 expression were observed in the BdCs, serum, and bone biopsies from the AS group. BIX-induced ER stress stimulated osteoblastic activity and IL-23 secretion by upregulating RUNX2 expression. Furthermore, in AS BdCs, RUNX2 interacted with C/EBPβ to bind to IL-23 promoter and RUNX2 knockdown suppressed IL-23 secretion. These finding may provide a molecular mechanism involved in sustained ER stress in AS BdCs stimulates the activation of RUNX2 and C/EBPβ genes, leading to IL-23 production.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Bones and its-derived cells from patients with AS showed an increase in ER stress. </LI> <LI> IL-23 cytokine was significantly higher in AS patients than in healthy controls. </LI> <LI> Inducing ER stress in AS exhibited an increase of bone-related genes. </LI> <LI> Inducing ER stress in AS was accompanied with augmentation of IL-23 cytokine. </LI> <LI> ER stress-induced RUNX2 is involved in IL-23 secretion and bone-related genes. </LI> </UL> </P>

Effects of <i>Ecklonia cava</i> ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: Role of suppressor of cytokine signaling

Kim, Se-Kwon,Lee, Da-Young,Jung, Won-Kyo,Kim, Ji-Hye,Choi, Inhak,Park, Sae-Gwang,Seo, Su-Kil,Lee, Soo-Woong,Lee, Chang Min,Yea, Sung Su,Choi, Yung Hyun,Choi, Il-Whan Elsevier 2008 BIOMEDICINE AND PHARMACOTHERAPY Vol.62 No.5

<P><B>Abstract</B></P><P><I>Ecklonia cava</I> (EC) is a brown alga that evidences radical scavenging activity, bactericidal activity, tyrosinase inhibitory activity, and protease inhibitory activity. However, its anti-allergic effects remain poorly understood. In the current study, we attempted to determine whether pretreatment with EC induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and airway luminal narrowing; the development of airway hyperresponsiveness; the detection of tumor necrosis factor-alpha (TNF-α) and Th2 cytokines, including IL-4 and IL-5 in the bronchoalveolar lavage (BAL) fluid; and the detection of allergen-specific immunoglobulin E (IgE) in the serum. However, the administration of EC extract prior to the final airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that EC extracts treatment resulted in significant reductions on matrix metalloproteinase-9 (MMP-9) and Suppressor of cytokine signaling-3 (SOCS-3) expression and a reduction in the increased eosinophil peroxidase (EPO) activity. The treatment of animals with EC extracts resulted in a significant reduction in the concentrations of the Th2 cytokine (IL-4 and IL-5) in the airways, without any concomitant increase in the concentration of Th1 cytokines. These findings indicate that EC extracts may prove useful as an adjuvant therapy for allergic airway reactions via the inhibition of the Th2 response. Accordingly, this study may provide evidence that EC extract performs a critical function in the amelioration of the pathogenetic process of asthma in mice.</P>

Effects of Melatonin and Its Underlying Mechanism on Ethanol-Stimulated Senescence and Osteoclastic Differentiation in Human Periodontal Ligament Cells and Cementoblasts

Bae, Won-Jung,Park, Jae Suh,Kang, Soo-Kyung,Kwon, Il-Keun,Kim, Eun-Cheol MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.6

<P>The present study evaluated the protective effects of melatonin in ethanol (EtOH)-induced senescence and osteoclastic differentiation in human periodontal ligament cells (HPDLCs) and cementoblasts and the underlying mechanism. EtOH increased senescence activity, levels of reactive oxygen species (ROS) and the expression of cell cycle regulators (p53, p21 and p16) and senescence-associated secretory phenotype (<I>SASP</I>) genes (interleukin [IL]-1β, IL-6, IL-8 and tumor necrosis factor-α) in HPDLCs and cementoblasts. Melatonin inhibited EtOH-induced senescence and the production of ROS as well as the increased expression of cell cycle regulators and SASP genes. However, it recovered EtOH-suppressed osteoblastic/cementoblastic differentiation, as evidenced by alkaline phosphatase activity, alizarin staining and mRNA expression levels of Runt-related transcription factor 2 (Runx2) and osteoblastic and cementoblastic markers (glucose transporter 1 and cementum-derived protein-32) in HPDLCs and cementoblasts. Moreover, it inhibited EtOH-induced osteoclastic differentiation in mouse bone marrow–derived macrophages (BMMs). Inhibition of protein never in mitosis gene A interacting-1 (PIN1) by juglone or small interfering RNA reversed the effects of melatonin on EtOH-mediated senescence as well as osteoblastic and osteoclastic differentiation. Melatonin blocked EtOH-induced activation of mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and Nuclear factor of activated T-cells (NFAT) c-1 pathways, which was reversed by inhibition of PIN1. This is the first study to show the protective effects of melatonin on senescence-like phenotypes and osteoclastic differentiation induced by oxidative stress in HPDLCs and cementoblasts through the PIN1 pathway.</P>

큰느타리버섯 균사체로 제조한 발효두부 추출물의 면역 활성

이상원(Sang-Won Lee),강종우(Jong-Woo Kang),김재용(Jae-Yong Kim),박경욱(Kyung-Wuk Park),박석규(Seok-Kyu Park),주옥수(Ok-Soo Joo),이성태(Sung-Tae Yee),서권일(Kwon-Il Seo) 한국식품영양과학회 2010 한국식품영양과학회지 Vol.39 No.1

두부의 기능성 및 저장성을 향상시킬 목적으로 큰느타리버섯 균사체를 이용한 발효두부를 제조하여 물과 메탄올로 추출하여 면역세포 활성에 미치는 효과를 조사하였다. 큰느타리버섯 균사체를 배양하기 위한 최적 배지는 PD broth 배지인 것을 확인하였으며, 큰타리버섯 균사체를 이용한 두부의 최적 발효기간은 7일 정도가 적당하였다. 큰느타리버섯 균사체를 이용하여 발효한 두부의 물 및 메탄올추출물은 0.01 ㎍/mL 농도 이상에서 비장세포의 증식을 유도하였으며, 이들 추출물은 IL-6, IFN-γ 분비를 유도하는 것으로 나타났다. 발효두부 물 추출물은 대조군에 비해 대식세포의 일산화질소 생산을 1 ㎍/mL 농도 이상에서 유의적으로 증가시키는 것을 알 수 있었으며, 메탄올 추출물은 10 ㎍/mL 농도 이상에서 그 생산을 증가시켰다. 발효두부 추출물들은 대식세포가 분비하는 IL-6, TNF-α, IL-1β 및 GM-CSF 분비량을 유의하게 증가시켰다. 따라서 큰느타리버섯 균사체로 발효한 두부는 기능성 두부로 개발이 가능하리라 생각된다. In order to improve the functional benefits and storage properties of soybean tofu, fermented tofu was developed using Pleurotus eryngii mycelia. The immune activities of water and methanol extracts of the tofu were investigated. The optimal medium for the growth of Pleurotus eryngii mycelia was PD broth medium and the optimal fermentation period for the tofu was 7 days. The water and methanol extracts of the fermented tofu induced the proliferation of spleen cells at above 0.01 ㎍/mL. The water extract increased IL-2, IFN-γ production, while the methanol extract increased IFN-γ synthesis. The water and methanol extracts of the fermented tofu induced the NO production in RAW264.7 macrophage cells at above 1 ㎍/mL and above 10 ㎍/mL concentration, respectively. The extracts also significantly increased the production of IL-6, TNF-α, IL-1β and GM-CSF in the cells. These results suggest that the tofu fermented with Pleurotus eryngii mycelia could be developed as a functional tofu.

숯첨가 사료투여가 넙치의 면역반응에 미치는 영향

권문경,이윤호,박상언,김봉석,박수일 한국어병학회 2002 한국어병학회지 Vol.15 No.1

숯첨가 사료 투여가 넙치에 미치는 영향을 알기 위하여, 넙치에 숯 1%, 3%, 5% 첨가사료를 8주간 투여하면서 성장, 혈액성분, 비특이적면역능을 분석하였으며 어병세균인 Edwardsiella tarda 균의 공격 시험에 대한 방어능을 조사하였다. 숯 첨가 사료 투여는 넙치의 성장과 라이소자임 활성에서는 유의적인 차이를 나타내지 못했지만, 5% 숯첨가구에서 혈액 중의 total protein과 cholesterol의 농도가 대조구에 비하여 낮게 나타났다. 그리고, 숯 3% 첨가구에서 두신 식세포의 활성 및 병원성 세균인 E. tarda에 대한 방어능도 가장 높게 나타났다. The charcoal effects on the immune responses of flounder, Paralichthys olivaceus were studied. Fish were fed an experimental diet supplemented with 1%, 3% or 5% of charcoal to a commercial diet. Several factors such as weight gain, hematological parameters, nonspecific immune responses and resistance against Edwardsiella tarda were evaluated 4 and 8 weeks after the administraion. The changes of body weight and lysozyme activities were not signigicant among tested groups. But cholesterol and total protein concentration in the blood were significantly lower in the 5% supplemented group than in the control. The production of superoxide by macrophage from the head kidney, examined by NBT reduction, was significantly higher in the 3% charcoal supplemented groups than in the control. The survival rate after an artificial challenge with 1×10^exp(7) cells of E. tarda per fish was significantly the highest in the 3% charcoal supplemented group.

넙치, Paralichthys olivaceus의 수온 자극 스트레스에 대한 사료첨가제 투여 효과

권문경,박상언,방종득,조병열,이상민,박수일 한국어병학회 2003 한국어병학회지 Vol.16 No.3

본 연구는 넙치의 수온 스트레스에 대한 사료첨가제 (미역 5%, 미역 10%, 어보산 0.5%, 고추냉이 잎 2%, 고추냉이 줄기 2%)의 영향을 혈액학적, 면역학적 측면과 Edwardsiella tanda를 사용하여 질병에 대한 저항성으로서 평가하였다. 혈장의 글루코즈와 콜티졸 농도는 1차 수온 변동 후 대조구에 비하여 미역 5%와 고추냉이잎 2% 첨가구에서 유의적으로 낮게 나타났다(P〈0.05). 1차 수온 변동 후 혈장 라이소자임 활성과 E. tarda의 공격 시험 후 생존율은 미역 5%첨가구에서 대조구에 비하여 유의적으로 높게 나타났다(P〈0.05). 본 실험 결과 미역 5% 첨가 사료 투여는 넙치의 스트레스 상태에서 질병 감염에 대한 저항성을 높일 수 있을 것으로 사료된다. The effect of each dietary supplements (Undaria 5%, Undaria l0%, Obosan 0.5%, Wasabi leaf 2%, Wasabi stem 2%) on the water temperature fluctuation in juvenile olive flounder (Puralichthys olivaceus) was investigated. The response to stress was assessed in terms of effects on haematological and immunological, and resistance against Edwurdsiella tarda infection. Plasma glucose and cortisol levels were significantly lower in 5% undaria and 2% wasabi leaf supplement groups than the controls after the first change of water temperature (P<0.05). The plasma lysozyme activities and the survival rates from E. tarda infection were significantly higher in the 5% undaria supplement groups than the control (P<0.05). These results suggest that the 5% undaria supplement seems to be contributable to the increased disease resistance on olive flounder.

세기변조방사선치료의 선량분포 검증에 관한 연구

권수일,신동호,송재영,안진호 京機大學校 2006 論文集 Vol.50 No.-

Film dosimetry as a part of patient specific intensity modulated radiation therapy quality assurance (IMRT QA) has been accomplished to develop the new optimization method of film isocenter offset and to suggest the new quantitative criteria for film doimetry after optimization. Five patients with head and neck cancers were measured in IMRT dosimetry by film method. Optimization method with the local minimum was developed to adjust the film isocenter offset error, which is the biggest part of systemic errors. The mean ratios were 5.33% and 7.09% for 5mm and 1 mm resolution dose data optimization respectively.

HFC-134a와 대체냉매 HFC-152a에 CF_3I를 혼합한 자동차냉매 특성

권일욱,박찬수,홍경한,문기선,최운수,서의경,윤갑식,이종인,하옥남 朝鮮大學校 機械技術硏究所 2002 機械技術硏究 Vol.5 No.1

These days, an attention of environment has been increasing all over the world. to prevent the green house effect and destruction of an ozone layer, an ozone destruction potential(ODP) be zero and a refrigerant for low global warming potential(GWP) is needed. HFC-134a, in which hydrogen is mixed instead of chlorine is a refrigerant used for automobile conditioners and its destruction potential is ecologically zero. However, it is not considered as a perfect substitutive refrigerant as its GWP is high. It is studied refrigerant mixtures in which HFC-134a, HFC-152a and CF_3I with low GWP and zero ODP are mixed by experimentally and concluded as follows; 1. with the variation of speed of compressor outside temperature and flow rate, the heat of evaporator and compressor and coefficient of performance was varied, and influenced the air conditioner. 2. The pressure of evaporator was decreased with increasing the speed of compressor and that of the refrigerant HFC-134a was higher 21% than that of azotrope refrigerant mixed with CF_3I. The overall capacity of condensor and evaporator was increased and HGC-134a was higher than azotrope refrigerant mixed with CF_3I 3. The capacity of evaporator with the refrigerant HFC-134a was higher 6% than azotrope refrigerant mixed with CF31 and the required power with zaotrope refrigerant mixed with CF_3I was higher 11% than that of HFC-134a. 4. The COP of the refrigerant FHC-134a was higher 31% in 1000RPM. when outside temperature was increased, COP was decreased. 5. Performance of HFC-134a is better than azotrope refrigerant mixed with CF_3I but prefered zaotrope refrigerant mixed with CF_3I considering the environment.

農業技術 弘報用 印刷媒體의 製作活用改善에 관한 硏究

金性洙,崔敏浩,鄭址雄,權一男 서울大學校 農科大學 1986 서울대농학연구지 Vol.11 No.1

The objectives of the study were to: 1) analyze the structure and styles of the printed media for agricultural information, 2) review the utilization of the magazine by farmers and extension workers, 3) survey the needs of subscribers for the printed media, 4) find ways for improvement in putting out the magazine, and 5) recommend effective methods for publication and utilization of the printed media. Data were collected by mail and group interview from 179 of the randomly sampled farmers and from 148 of the extension agents in selected areas in Korea. The data were analyzed by HP 3000 computer in the College of Agriculture, Seoul National University. Major statistical techniques used for the study were frequency distrbution, percentile. The results of the study were as follows: 1. Communication exposure of the farmers to the printed media was lower than that of the extension agents, however the level of exposure was considerably high considering limited number of copy for farmers. 2. Farmers' major channel for acquisition of new farming technology was personal communication with extension agents, and extension agents' major channel for advanced technology was printed media. 3. It was revealed that the farmers did not have any difficulty in understanding contents of the printed media. 4. The printed media had been providing long range information for the farmers and extension agents. The farmers and extension agents responded that the consistency in the table of contents and the articles was good, and they liked the idea of emphasis by adopting the box style editing. 5. The farmers responded that the topics of the magazine should reflect the current change in agriculture. 8. The farmers responded that they would like to see articles on horticulture and successful case stories in farming. 9. The farmer-subscriber fully utilized information on farming and rural life in the printed media. Extended distrubution of the printed media would be necessary to enlarge the benefit from the advanced farming technology and improved rural home life.