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>

GM-CSF Promotes Antitumor Immunity by Inducing Th9 Cell Responses

Kim, Il-Kyu,Koh, Choong-Hyun,Jeon, Insu,Shin, Kwang-Soo,Kang, Tae-Seung,Bae, Eun-Ah,Seo, Hyungseok,Ko, Hyun-Ja,Kim, Byung-Seok,Chung, Yeonseok,Kang, Chang-Yuil American Association for Cancer Research 2019 Cancer immunology research Vol.7 No.3

<P>Granulocyte-macrophage colony-stimulating factor (GM-CSF) functions as an adjuvant for antitumor immunity through an unclear mechanism. By activating monocyte-derived dendritic cells, GM-CSF induces Th9 development and IL9 production, which facilitates antitumor cytotoxic T lymphocyte responses.</P><P>GM-CSF as an adjuvant has been shown to promote antitumor immunity in mice and humans; however, the underlying mechanism of GM-CSF–induced antitumor immunity remains incompletely understood. In this study, we demonstrate that GM-CSF potentiates the efficacy of cancer vaccines through IL9-producing Th (Th9) cells. GM-CSF selectively enhanced Th9 cell differentiation by regulating the COX2–PGE<SUB>2</SUB> pathway while inhibiting the differentiation of induced regulatory T (iTreg) cells <I>in vitro</I> and <I>in vivo</I>. GM-CSF–activated monocyte-derived dendritic cells converted tumor-specific nai¨ve Th cells into Th9 cells, and delayed tumor growth by inducing antitumor CTLs in an IL9-dependent manner. Our findings reveal a mechanism for the adjuvanticity of GM-CSF and provide a rationale for the use of GM-CSF in cancer vaccines.</P>

들깨(Perilla frutescens) 새싹 추출물의 항산화 및 항염 효과

정승일(Seung-Il Jeong),김현수(Hyeon Soo Kim),전인화(In Hwa Jeon),강현주(Hyun Ju Kang),목지예(Ji Ye Mok),천춘진(Chun Jin Cheon),유현희(Hyeon Hee Yu),정선일(Seon Il Jang) 한국식품과학회 2014 한국식품과학회지 Vol.46 No.1

본 연구는 들깨 새싹 추출물의 항산화, 항염증 및 항부종에 대한 효과를 조사하였다. 들깨 새싹 추출물은 DPPH와 ABTS 라디칼을 효과적으로 제거하는 항산화 활성이 우수하였다. 또한 들깨 새싹 추출물은 활성화된 설치류 유래 대식세포주인 RAW 264.7세포와 인간 유래 HMC-1 세포의 TNF-α와 IL-1β를 효과적으로 억제하였다. 더욱이 마우스의 귀와 발 부종을 억제하는 우수한 효과가 있었다. 이러한 결과는 들깨 새싹 추출물은 항산화제로 사용될 수 있을 뿐만 아니라 항염증과 항부종에 효과적인 물질이라는 것을 제시해주었다. 이와 관련된 들깨 새싹 추출물의 기능성에 대해서는 앞으로 분자생화학적 수준에서 더 연구해야할 필요성이 있는 것으로 사료된다. We investigated the effects of an ethanol extract from Perilla frutescens sprouts (PFSE) as an antioxidant, and its effects on edema and inflammation in RAW 264.7 cells and HMC-1 cells. The antioxidant activities (DPPH and ABTS radical scavenging) of PFSE were similar to those of butylated hydroxytoluene (BHT) and (±)-6-hydroxy-2,5,7,8- tetramethylchromane-2-carboxylic acid (Trolox). We also investigated the anti-inflammatory effects of PFSE on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and HMC-1 cells stimulated with phorbol 12-myristate 13-acetate (PMA) with the calcium ionophore A23187. TNF-α and IL-1β production, which had been increased by treatment with LPS or PMA plus A23187, were significantly inhibited by PFSE in a dose-dependent manner. Furthermore, PFSE significantly reduced the xylene-induced ear edema and the carrageenan-induced paw edema of ICR mice in a dosedependent manner. The effects of PFSE (200 mg/kg) in reducing ear and paw edema were similar to those of aspirin (50mg/kg). These results suggest that PFSE can be potentially used as a medicine for treating oxidative stress, an edematous and inflammatory disease.

Tumor Necrosis Factor-α-Activated Human Adipose Tissue–Derived Mesenchymal Stem Cells Accelerate Cutaneous Wound Healing through Paracrine Mechanisms

Heo, Soon Chul,Jeon, Eun Su,Lee, Il Hwan,Kim, Hoon Soo,Kim, Moon Bum,Kim, Jae Ho The Society for Investigative Dermatology, Inc 2011 The Journal of investigative dermatology Vol.131 No.7

Human adipose tissue–derived mesenchymal stem cells (ASCs) stimulate regeneration of injured tissues by secretion of various cytokines and chemokines. Wound healing is mediated by multiple steps including inflammation, epithelialization, neoangiogenesis, and proliferation. To explore the paracrine functions of ASCs on regeneration of injured tissues, cells were treated with tumor necrosis factor-α (TNF-α), a key inflammatory cytokine, and the effects of TNF-α-conditioned medium (CM) on tissue regeneration were determined using a rat excisional wound model. We demonstrated that TNF-α CM accelerated wound closure, angiogenesis, proliferation, and infiltration of immune cells into the cutaneous wound in vivo. To assess the role of proinflammatory cytokines IL-6 and IL-8, which are included in TNF-α CM, IL-6 and IL-8 were depleted from TNF-α CM using immunoprecipitation. Depletion of IL-6 or IL-8 largely attenuated TNF-α CM-stimulated wound closure, angiogenesis, proliferation, and infiltration of immune cells. These results suggest that TNF-α-activated ASCs accelerate cutaneous wound healing through paracrine mechanisms involving IL-6 and IL-8.

Effective Microorganism Substance (EM-S) Reduces Development and Aggravation of Atopic Dermatitis-like Skin Lesions in NC/Nga Mice

Park, Kwang-Hyun,Jeong, Seung-Il,Mok, Ji-Ye,Cho, Jung-Keun,Park, Ji-Min,Jeon, In-Hwa,Kim, Hyeon-Soo,Jang, Seon-Il The Korean Society for Applied Biological Chemistr 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.2

In a previous study, our group showed that the effective microorganism substance (EM-S) produced by fermentation of medicinal plants with effective microorganisms has an antiinflammatory effect on atopic dermatitis-like lesions in NC/Nga mice. However, the possible antiinflammatory effect and skin barrier function of EM-S for inflammatory cell infiltration, Interleukin-4 (IL-4) production, C-C chemokine receptor 10 (CCR10), and filaggrin (FLG) expression were not reported. Therefore, effects of EM-S on the development of atopic dermatitislike skin lesions in NC/Nga mice were evaluated. Efficacy of EM-S was judged by measurement of scratching behavior, T-cell subset infiltration, cytokine production, and FLG expression. Topical application of EM-S significantly reduced scratching behavior in NC/Nga mice caused by house dust mite antigen (Dermatophagoides farinse extract, DfE) sensitization. IL-4 production and $CD4^+$ and $CD45^+$ cell infiltrations were significantly reduced by EM-S. CCR10 expression was also significantly inhibited by EM-S. EM-S treatment also increased the level of FLG reduced by DfE sensitization. These results demonstrate EM-S, when applied topically, may be an effective substance for management of atopic dermatitis patients.

The Lipopolysaccharide from Porphyromonas gingivalis Induces Vascular Permeability

Su-Ryun Kim,Seong-Kyoon Jeong,Woo-Sik Kim,Hwa-Jin Jeon,Hyun-Joo Park,Mi-Kyoung Kim,Hye-Ock Jang,Il Yun,Soo-Kyung Bae,Moon-Kyoung Bae KOREAN ACADAMY OF ORAL BIOLOGY 2011 International Journal of Oral Biology Vol.36 No.1

Porphyromonas gingivalis, one of the major periodontal pathogens, is implicated in the initiation and progression of periodontal disease. The initial stages of periodontal inflammation are accompanied by vascular hyperpermeability. In our present study, we report that the P. gingivalis lipopolysaccharide (LPS) increases the mRNA expression of interleukin-8 (IL-8), a major inducer of vascular permeability, in vascular endothelial cells. P. gingivalis LPS also stimulated the induction of IL-8 secretion in endothelial cells. The P. gingivalis LPS-induced expression of IL-8 was primarily modulated by nuclear factor-κB (NF-κB). P. gingivalis LPS significantly enhanced the vascular permeability both in vitro and in vivo, and a blockade of the IL-8 receptor decreased the P. gingivalis LPS-induced vascular permeability. Taken together, these results suggest that P. gingivalis LPS increases vascular permeability through the NF-κBdependent production of IL-8 in vascular endothelial cells.

行政責任과 倫理問題에 관한 硏究

田秀一 光云大學校 1986 論文集 Vol.15 No.-

The most important issue in modern democracy is to ensure a responsible government or responsible public servants. The responsibility in government cannot be stressed too much. This study is concerned with the theoretical framework for ensuring of personal responsibility on the ethical basis. This article is composed of six chapters. ChapterⅠ is the introduction part in which the objective of the study and its content and methodology are described. ChapterⅡ provides an analytical perspective on responsibility; its controversial meaning and connotations in which we speak of responsibility. ChapterⅢ deals with the objects and criteria of administrative responsibility. This chapter examines the evolving view point on responsibility; to whom or for what public administrators are responsible. ChapterⅣ focuses on problems of responsibility in the exercise of discretionary power. Public administrators do indeed exercise decreation, but we view this fact misgivings. The reason is that it seems to introduce an element of uncertainty into the standards by which we would judge a bureaucrat's conduct. But we must recognize that without discretionary power, that is, without the capacity to choose and make decisions, the bureaucrat could not be responsible at all. ChapterⅤ examines some ethical problems in the enforcement of responsibility. Ethical issues arise in many different forms for public administrators, but in each instance difficult questions of administrative responsibility are raised. Conflicts of responsibility are the ways in which ethical dilemmas are typically experienced by public administrators. It represents conflicts between public role and self-interest. ChapterⅥ is the conclusion part in which I would like to stress in the importance of inner control instead of outside control for the enforcement of administrative responsibility. Responsibility is the power of a particular private code of morals to control the conduct of the individual in the presence of strong desires or impulses.

객체 지향 데이타베이스를 위한 객체들의 효율적인 집중화

全日秀 慶一大學校 1993 論文集 Vol.9 No.1

Clustering is an effective mechanism for retrieving objects in an object-oriented databases. Although various clustering schemes were proposed in the object-oriented databases literature, all of them use only one relationship of an object-oriented data model in order to cluster complex objects. This paper proposes an effective clustering scheme which uses both generalization/specialization and aggregation relationship under the core object-oriented data model. The proposed clustering scheme performs clustering in two steps ; the first step is clustering of the class hierachy, and the second step is clustering of the class composition hierachy of the core model. This paper also provides the performance analysis of the proposed clustering shceme by simulation.

유육종증 1례

전수영,정운태,황성보,류종철,최수전,고일향 인제대학교 1993 仁濟醫學 Vol.14 No.4

저자들은 폐결핵 추정하에 치료를 받았던 Sarcoidosis 환자 1례를 경험했기에 문헌적 고찰과 함께 보고하는 바이다. Sarcoidosis is a granulomatous disease of unknown etiology In which pulmonary manifestations typically predominate with protean extrapulmonary and systemic manifestations. In sarcoidosis, pulmonary symptoms include dyspnea on exertion, non-productive cough and wheezing. Typical radiologic finding is a diffuse infiltration with or without bilateral symmetric hilar lymphadenopathy. Sarcoidosis should be differentiated with pulmonary tuberculosis because of its clincal and radiological slmilarity in Korea, an endemic area of pulmonary tuberculosis. We report a case of sarcoidosis patient whose symptoms were not improved by treatment with anti-tuberculous medication, but by steroid therapy following the diagnosis of sarcoidosis made by biopsy.

우리나라 電子工業 育成方向에 對한 硏究

田秀一,宋甲鎔 光云大學校 1974 論文集 Vol.3 No.-

The present century is characterized by the Electronic Age indebted to the remarkable advancement of the electronic technique and the enlargement of its application sphere from our daily life to the space development especially since World War Ⅱ. In a word, the electronic industry is regarded as the labor and brain-intensive industry which has ahigher additional value than anything else. It was the latter half of 1960s that the newest technique-integrated industry has come before footlights in Korea. The advanced nations in electronic industry are willingly to render oversea investments to the under-developed, or the developing countries which have inexpensive and abundant man power. As a result of this tendency, the electonic industries in all over the world are on the trend of international division of labors, and in proportion to the advancement of electronic skill, the extent of the division of labor will be great as much in future. Considering a characteristics of the electronic industry and its contribution to the national economic growth, our country is obviously proved to have various beneficial and pertinent situations as far as electronic industries are concerned. In this context, our country has nominated the electronic goods as a strategic export oriented industry since the beginning of 1970s, and established a long-term planning for developing of the electronic industries of Korea, making great strides with strenuous efforts for the planned task that the electronic department only must occupy 250 million dollars among the amount of total export goal, 10billion dollars in the year of 1980. Having attempted to make a general survey on the present state of the electronic industries in Korea, we suggested a dissenting opinion to the Koreanized concept of the raw materials which are constructed to coincide with accessory parts or intermediate manufactured goods. It is attributable to the fact that the electronic kernel skill of Korea remains so far at the low level. We think the current concept of the raw materials will have to be changed according to the development of the electronic technique in the near future. On touched on the present condition of the production and employment structure, the export-import system, and in addition, the inducement of foreign capital and technique, including the trend of international market for electronic manufactured goods. In this thesis, we are greatly interested in examining and analyzing our gevernment policies on the basis of the theory of economics, which practised so far according to the long-term electronic industry development planning. Above all, the emphasis is placed on finding out the urgent problems and their possible plans disclosed as a result of this study. The most important task to be inevitably accomplished by the end of 1970s is to proceed on the stage to make electronic machinery and tools for industrial world, which have the highest additional value, passing from the current production stage of accessory parts or electronic manufactured goods for family use. In addition to the enhancement of the electronic technical standard, we must take into consideration to expand international export markets by means of the application of Korean native design to all the export-oriented goods and so on. To sum up, it is timely and properly estimated that our goverment nominated the electronic industry as a strategic export-oriented industry and the government measures executed in compliance with the long term development planning. It is also desired to carry out the measures for promoting electronic industries by the government initiative, for the time being. In proportion to this, the fulfilment of administrative responsibility for it will be strongly required. At the same time, we proposed to establish a synthetic research center in charge of driving harmoniously man power planning for supply and demand, development researches by means of the industry- education cooperation.