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.

저강도 초음파 및 레이저를 이용한 장관골 불유합의 치료

전인호,오창욱,김성중,경희수,박일형,박병철,인주철,여준영 대한골절학회 2003 대한골절학회지 Vol.16 No.2

목 적: 저강도 초음파는 인체 및 동물 실험에서 골조직에 낮은 미세한 물리적 압력을 가하여 골절의 치유에 유리한 영향을 주고, 레이저 (LASER)는 심부 조직에 혈류를 증가시키고, 세포 내 잠재된 에너지를 증가시키는 것으로 알려져 있다. 이에 저자들은 임상적으로 확진된 장관골 붕류합의 치료에 있어 펄스형 저강도 초음파와 레이저를 적용하고 그 효용성을 알아보고자 하였다. 대상 및 방법: 초음파/레이저의 치료 효과를 비교하기 위하여 장관골 불유합으로 확진된 16예 중 8예는 연구군으로 골이식술 후 저강도 초음파와 레이저 치료를 추가하였고 대조군 8예에 대해선 일반적인 골이식술만 시행하여 조사하였다. 남자가 11예, 여자가 5예, 평균 연령은 41.7세 (19~62세)였고, 불유합 부위는 대퇴골이 10예, 경골이 6예였다. 첫 수상으로 인한 골절 후 초음파/레이저 치료까지 시간(골절 연력)은 평균 502일이었다. 결 과: 8예의 연구군에서는 완전 골유합이 6예에서 이루어졌으며 유합까지의 시간은 평균 141일 (101~202일)로 나타난 반면, 8례ㅢ 대조군에서는 5예에서 골유합이 이루어졌고, 유합까지의 시간은 평균 240일 (183~283일)이었다. 결 론: 저강도 초음파/레이져 골절 치료기가 반복된 수술로 인한 난치성 장관골 불유합의 치료에 있어 골이식술과 함께 사용될 경우 긍정적인 효과가 있었고, 특히 최초 가골 형성에 있어 대조군에 비해 그 시간을 줄일 수 있었따. Purpose: Low-intensity, pulsed ultrasound (LIPUS) has demonstrated a stimulation and acceleration of the normal fracture-repair process in cellular bases as well in animal and human models. In this study, the adjunctive effect of LIPUS and LASER was investigated in established nonunion of the long bones. Materials and Methods: Study group consisted of eight patients to whom conventional bone graft and adjunctive LIPUS and LASER was applied. On the other hands, eight patients in the control group underwent bone graft only. Eleven men and five women were included in this study and the average age of the patients was 41.7 years (range, 19~62 years). Six of the tibias and ten of the femurs met the criteria for established nonunion. The average fracture age, the post-fracture period before the start of LIPUS/LASER treatment, was 502 days. Results: Seven of the ten nonunions who were treated by LIPUS and LASER healed completely in an average treatment time of 141 days (range, 101~202 days) and otherwise, in control group, five of the eight nonunions healed completely, in 240 days (range 183~283 days). Conclusion: This clinical study showed a positive effect of LIPUS and LASER on the rate of osseous repair, especially accelerated time to initial callus cortical bridging compared to that of conventional treatment.

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.

한국영화의 시점과 화자연구 : 박광수의 <아름다운 청년 '전태일'>을 중심으로

전수일 경성대학교 1998 論文集 Vol.19 No.1

This thesis emphasize on the expression method of the 'point of view' and the 'narrator' through the analysis of decoupage on <A single spark 아름다운 청년 '전태일'> directed by Park, Kwang-Su, which is mentioned as the most representative one of realism film in Korean. The 'point of view' and the 'narrator' play a role of the objective alienation which originated from the process that history is restored and resurrected through the film. They motivates the conversion of tense and help all of the audiance take part in film as a historical observer and a participant in narrative structure. Accordinally, if focus on 'point of view of director who viewing Jeon, Tae-II through the writer in the film, Kim, Young-Su' by means of the cohesion with narrator's regard and director's on in park dealing with 'that way of converting tense(present and past) on the film named <A single park>. Also, it is clarified that the converting tense can be commented as the abjectivity of point of view through the changing color(color and black and white). Lastly, this article is for understanding the present step of realism on Korean cinema with the cinematic techinic of 'long-take' and 'plan-sequence, which are the expression method of 'point of view' and the 'narrator'.

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.