스포츠 현장에서 사고 분쟁해결을 위한 법적 구조 및 그 효용성 분석

박형상,육조영,김우규,이재봉,유관호,이무연,박태민,이신언 한국스포츠리서치 2005 한국 스포츠 리서치 Vol.16 No.2

1. The purpose of this study is to reflect reality of sports to legal structure. This author classified types of sports related accidents as match accidents, school accidents, leisure and living sports accidents. Out of such accidents common factors such as 'the provider of virtue' and 'user' could be deduced and this author reviewed what kinds of obligations must be shouldered by these people respectively. In particular this author stressed the fact that disproportionate emphasis is placed on malfeasance in disposition of dispute over the sports accidents. Malfeasance is a method for seeking relief through money after the accident. However default in an obligation enables supplementary completion when it is not performed or imperfectly performed. Thus if object which must be performed is providing safety then it is possible to secure safety prior to accident. Furthermore at such time mistake of the debtor can not become a factor. For this reason this line of thinking has the following merits: (1) In comparison with constitution of malfeasance default of an obligation has long prescription. It seems that such fact was a motivation for saving obligation for safety consideration by making it fall under the principle of faith. (2) Default of an obligation is not an obligation for ordinary attention which is cause of malfeasance but it takes up issue with obligation for attention required for performance. Game organization, sponsor and spectators etc. shares certain sense of identity and are demanded to have manners. As method for evaluation of such relationship of faith it may be possible to impose a special kind of obligation for attention and it will be close to constitution of default of an obligation. (3) Imposing obligation for provision clarifies that such responsibility belongs to game organizations promoting sports to which anyone can participates or to national or public organizations, sponsor, schools which induced such sports as a part of its educational programs, installer who made people use it as leisure facility or person in charge for its management. (4) It is also applicable to umpires, players or spectators who use field of sports. It is possible to reflect reality whereby these people specifically relate themselves to sports. In consequence it will be possible to make people feel the necessity of expanding the principals of sports from 'doers' to 'watchers.' (5) The obligation of provision is an obligation under the principle of faith therefore mutual negotiation may be expected to clarify such fact. It may be also evaluated by effectuation of users' self-determining right. 2. If the above mentioned structure is provided then, although it is limited to sports, students who are subjects of instruction, seminar attendants, and furthermore players who finished games may be obligated to bear responsibility for safety consideration under the principle of faith. Accordingly level of relief for considerable number of victims may be increased as cases of treating even borrowed materials as default of obligation being expanded. 3. As scope of responsibility becomes more clearer it will be possible to prevent disputes while securing more safety as rules and regulations become more clearly enacted or new contract is signed or existing contract is revised.

Toll-like Receptors and Innate Immunity

Yuk, Jae-Min,Jo, Eun-Kyeong The Korean Society for Microbiology 2011 Journal of Bacteriology and Virology Vol.41 No.4

Toll-like receptors (TLRs) are the best-characterized membrane-bound receptors in innate immune cells, including macrophages and dendritic cells. Upon recognition of specific ligands originating from pathogen- and modified self-derived molecules, TLRs trigger intracellular signaling cascades that involve various adaptor proteins and enzymes, resulting in the generation of proinflammatory and antimicrobial responses through the activation of transcription factors such as nuclear factor-${\kappa}B$. TLR-dependent signaling pathways are tightly regulated during innate immune responses by a variety of negative regulators. This review focuses on the newly described regulation of TLR-dependent signaling pathways, and emphasizes the roles of TLRs in innate immunity. Efforts to modulate these regulatory pathways and signaling molecules may result in the development of new therapeutic strategies through TLR-based therapy.

Bacillus calmette-guerin cell wall cytoskeleton enhances colon cancer radiosensitivity through autophagy.

Yuk, Jae-Min,Shin, Dong-Min,Song, Kyoung-Sub,Lim, Kyu,Kim, Ki-Hye,Lee, Sang-Hee,Kim, Jin-Man,Lee, Ji-Sook,Paik, Tae-Hyun,Kim, Jun-Sang,Jo, Eun-Kyeong Landes Bioscience 2010 AUTOPHAGY Vol.6 No.1

<P>The cell wall skeleton of Mycobacterium bovis Bacillus Calmette-Guerin (BCG/CWS) is an effective antitumor immunotherapy agent. Here, we demonstrate that BCG/CWS has a radiosensitizing effect on colon cancer cells through the induction of autophagic cell death. Exposure of HCT116 colon cancer cells to BCG/CWS before ionizing radiation (IR) resulted in increased cell death in a caspase-independent manner. Treatment with BCG/CWS plus IR resulted in the induction of autophagy in colon cancer cells. Either the autophagy inhibitor 3-methyladenine or knockdown of beclin 1 or Atg7 significantly reduced tumor cell death induced by BCG/CWS plus IR, whereas the caspase inhibitor z-VAD-fmk failed to do so. BCG/CWS plus IR-mediated autophagy and cell death was mediated predominantly by the generation of reactive oxygen species (ROS). The c-Jun NH(2)-terminal kinase pathway functioned upstream of ROS generation in the induction of autophagy and cell death in HCT116 cells after co-treatment with BCG/CWS and IR. Furthermore, toll-like receptor (TLR) 2, and in part, TLR4, were responsible for BCG/CWS-induced radiosensitization. In vivo studies revealed that BCG/CWS-mediated radiosensitization of HCT116 xenograft growth is accompanied predominantly by autophagy. Our data suggest that BCG/CWS in combination with IR is a promising therapeutic strategy for enhancing radiation therapy in colon cancer cells through the induction of autophagy.</P>

Role of apoptosis‐regulating signal kinase 1 in innate immune responses by <i>Mycobacterium bovis</i> bacillus Calmette‐Guérin

Yuk, Jae‐,Min,Shin, Dong‐,Min,Yang, Chul‐,Su,Kim, Ki Hye,An, Se‐,Jin,Rho, Jaerang,Park, Jeong‐,Kyu,Jo, Eun‐,Kyeong Nature Publishing Group 2009 Immunology and cell biology Vol.87 No.1

<P><I>Mycobacterium bovis</I> bacillus Calmette‐Guérin (BCG) induces innate immune responses through Toll‐like receptor (TLR) 2 and TLR4. We investigated the role of apoptosis‐regulating signal kinase (ASK) 1 in reactive oxygen species (ROS)‐mediated innate immune responses induced by BCG mycobacterial infection. In macrophages, <I>M. bovis</I> BCG stimulation resulted in rapid activation of mitogen‐activated protein kinases (MAPKs), secretion of inflammatory cytokines, such as tumor necrosis factor (TNF)‐α and interleukin (IL)‐6, and ROS generation in a TLR2‐ and TLR4‐dependent manner. <I>M. bovis</I> BCG‐induced ROS production led to robust activation of ASK1 upstream of the c‐jun‐N‐terminal kinase and p38 MAPK, but not extracellular‐regulated kinase 1/2. Blocking ASK1 activity markedly attenuated <I>M. bovis</I> BCG‐induced TNF‐α and IL‐6 production by macrophages. Both TLR2 and TLR4 were required for optimal activation of ASK1 in response to <I>M. bovis</I> BCG. Furthermore, we present evidence that TNF receptor‐associated factor (TRAF) 6 activities were essential for ROS‐mediated ASK1 activation by <I>M. bovis</I> BCG. Finally, ASK1 activities were required for effective control of intracellular mycobacterial survival. Thus, the results of this study suggest a novel role of the TLR–ROS–TRAF6–ASK1 axis in the innate immune response to mycobacteria as a signaling intermediate.</P>

Vitamin D3 Induces Autophagy in Human Monocytes/Macrophages via Cathelicidin

Yuk, Jae-Min,Shin, Dong-Min,Lee, Hye-Mi,Yang, Chul-Su,Jin, Hyo Sun,Kim, Kwang-Kyu,Lee, Zee-Won,Lee, Sang-Hee,Kim, Jin-Man,Jo, Eun-Kyeong Elsevier 2009 Cell host & microbe Vol.6 No.3

<P><B>Summary</B></P><P>Autophagy and vitamin D3-mediated innate immunity have been shown to confer protection against infection with intracellular <I>Mycobacterium tuberculosis</I>. Here, we show that these two antimycobacterial defenses are physiologically linked via a regulatory function of human cathelicidin (hCAP-18/LL-37), a member of the cathelicidin family of antimicrobial proteins. We show that 1,25-dihydroxyvitamin D3 (1,25D3), the active form of vitamin D, induced autophagy in human monocytes via cathelicidin, which activated transcription of the autophagy-related genes <I>Beclin-1</I> and <I>Atg5</I>. 1,25D3 also induced the colocalization of mycobacterial phagosomes with autophagosomes in human macrophages in a cathelicidin-dependent manner. Furthermore, the antimycobacterial activity in human macrophages mediated by physiological levels of 1,25D3 required autophagy and cathelicidin. These results indicate that human cathelicidin, a protein that has direct antimicrobial activity, also serves as a mediator of vitamin D3-induced autophagy.</P>

Toll-like Receptors and Innate Immunity

Jae-Min Yuk,Eun-Kyeong Jo 대한미생물학회 2011 Journal of Bacteriology and Virology Vol.41 No.4

The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors

Yuk, Jae-Min,Shin, Dong-Min,Lee, Hye-Mi,Kim, Jwa-Jin,Kim, Sun-Woong,Jin, Hyo Sun,Yang, Chul-Su,Park, Kyeong Ah,Chanda, Dipanjan,Kim, Don-Kyu,Huang, Song Mei,Lee, Sang Ki,Lee, Chul-Ho,Kim, Jin-Man,Song Nature Publishing Group, a division of Macmillan P 2011 Nature immunology Vol.12 No.8

The orphan nuclear receptor SHP (small heterodimer partner) is a transcriptional corepressor that regulates hepatic metabolic pathways. Here we identified a role for SHP as an intrinsic negative regulator of Toll-like receptor (TLR)-triggered inflammatory responses. SHP-deficient mice were more susceptible to endotoxin-induced sepsis. SHP had dual regulatory functions in a canonical transcription factor NF-觀B signaling pathway, acting as both a repressor of transactivation of the NF-觀B subunit p65 and an inhibitor of polyubiquitination of the adaptor TRAF6. SHP-mediated inhibition of signaling via the TLR was mimicked by macrophage-stimulating protein (MSP), a strong inducer of SHP expression, via an AMP-activated protein kinase??dependent signaling pathway. Our data identify a previously unrecognized role for SHP in the regulation of TLR signaling.

TNF in Human Tuberculosis: A Double-Edged Sword

Yuk Jae-Min,Kim Jin Kyung,Kim In Soo,Jo Eun-Kyeong 대한면역학회 2024 Immune Network Vol.24 No.1

TNF, a pleiotropic proinflammatory cytokine, is important for protective immunity and immunopathology during Mycobacterium tuberculosis (Mtb) infection, which causes tuberculosis (TB) in humans. TNF is produced primarily by phagocytes in the lungs during the early stages of Mtb infection and performs diverse physiological and pathological functions by binding to its receptors in a context-dependent manner. TNF is essential for granuloma formation, chronic infection prevention, and macrophage recruitment to and activation at the site of infection. In animal models, TNF, in cooperation with chemokines, contributes to the initiation, maintenance, and clearance of mycobacteria in granulomas. Although anti-TNF therapy is effective against immune diseases such as rheumatoid arthritis, it carries the risk of reactivating TB. Furthermore, TNF-associated inflammation contributes to cachexia in patients with TB. This review focuses on the multifaceted role of TNF in the pathogenesis and prevention of TB and underscores the importance of investigating the functions of TNF and its receptors in the establishment of protective immunity against and in the pathology of TB. Such investigations will facilitate the development of therapeutic strategies that target TNF signaling, which makes beneficial and detrimental contributions to the pathogenesis of TB.

고려홍삼으로부터 분리한 compound K 함유분획에 의한 대식세포의 toll-like receptor-의존성 신호전달로 활성조절 분석

양철수,고성룡,조병구,이지연,김기혜,신동민,육재민,손현수,김영숙,위재준,도재호,조은경,Yang, Chul-Su,Ko, Sung-Ryong,Cho, Byung-Goo,Lee, Ji-Yeon,Kim, Ki-Hye,Shin, Dong-Min,Yuk, Jae-Min,Sohn, Hyun-Joo,Kim, Young-Sook,Wee, Jae-Joon,Do, Jae-Ho 고려인삼학회 2007 Journal of Ginseng Research Vol.31 No.4

본 연구에서는 고려홍삼으로부터 새로 분리한 CK 함유분획을 이용하여 마우스 대식세포에 대한 선천면역반응 조절에 미치는 영향을 조사하였다. 본 연구에서 사용된 농도의 CK 함유분획에서는 세포독성 효과가 관찰되지 않았으며 CK함유 분획의 전처리에 의하여 그람음성세균의 LPS, 또는 CpG-ODN에 의해 유도되는 NF-${\kappa}B$와 MAPK 활성 및 전염증성 사이토카인, NO의 분비가 TLR4 및 TLR9 특이적으로 억제되었다. 이와 같은 결과는 CK 함유분획이 TLR4을 매개로하는 염증반응뿐만 아니라 TLR9을 통한 염증반응에도 영향을 미치는 것으로 해석된다. 따라서 앞으로 CK 함유 분획에 포함된 개별 사포닌 등 시료 성분에 대한 면밀한 분석, 그리고 이들 개별 물질이 각각의 신호전달 체계에 미치는 영향과 그 기작에 대한 연구가 더욱 필요할 것으로 사료되며 염증억제제로서의 개발 가능성을 탐구하기 위한 생체 내에서의 효능 및 작용기전 분석이 요구된다. Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases 1/2 and p38], NF-${\kappa}B$, and expression of pro-inflammatory cytokines tumor necrosis factor-${\alpha}$, and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dose-dependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF-${\kappa}B$ activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9-associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4 and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.

고려홍삼으로부터 분리한 compound K 함유분획에 의한 대식세포의 toll-like receptor-의존성 신호전달경로 활성조절 분석

양철수(Chul-Su Yang),고성룡(Sung-Ryong Ko),조병구(Byung-Goo Cho),이지연(Ji-Yeon Lee),김기혜(Ki-Hye Kim),신동민(Dong-Min Shin),육재민(Jae-Min Yuk),손현주(Hyun-Joo Sohn),김영숙(Young-Sook Kim),위재준(Jae-Joon Wee),도재호(Jae-Ho Do),조은경 고려인삼학회 2007 Journal of Ginseng Research Vol.31 No.3

본 연구에서는 고려홍삼으로부터 새로 분리한 CK 함유분획을 이용하여 마우스 대식세포에 대한 선천면역반응 조절에 미치는 영향을 조사하였다. 본 연구에서 사용된 농도의 CK 함유분획에서는 세포독성 효과가 관찰되지 않았으며 CK 함유 분획의 전처리에 의하여 그람음성세균의 LPS, 또는 CpGODN에 의해 유도되는 NF-κB와 MAPK 활성 및 전염증성 사이토카인, NO의 분비가 TLR4 및 TLR9 특이적으로 억제되었다. 이와 같은 결과는 CK 함유분획이 TLR4을 매개로하는 염증반응뿐만 아니라 TLR9을 통한 염증반응에도 영향을 미치는 것으로 해석된다. 따라서 앞으로 CK 함유 분획에 포함된 개별 사포닌 등 시료 성분에 대한 면밀한 분석, 그리고 이들 개별 물질이 각각의 신호전달 체계에 미치는 영향과 그 기작에 대한 연구가 더욱 필요할 것으로 사료되며 염증 억제제로서의 개발 가능성을 탐구하기 위한 생체 내에서의 효능 및 작용기전 분석이 요구된다. Compound K (CK), a protopanaxadiol ginsenoside metabolite, was previously shown to have immunomodulatory effects. In this study, we isolated the CK rich fractions (CKRF) from Korean Red Ginseng and investigated the regulation of CKRF-mediated inflammatory signaling during Toll-like receptor (TLR)-mediated cellular activation. Among various TLR ligands, CKRF considerably abrogated TLR4- or TLR9-induced inflammatory signaling. Both LPS and CpG-containing oligodeoxynucleotides (CpG-ODN) stimulation rapidly activates mitogen-activated protein kinases [MAPKs; extracellular signal-regulated kinases ½ and p38], NF-κB, and expression of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6 in murine bone marrow-derived macrophages (BMDMs) in a time- and dosedependent manner. Of interest, pre-treatment of CKRF in either LPS/TLR4- or CpG-ODN/TLR9-stimulated macrophages substantially attenuated the LPS-induced inflammatory cytokine production and mRNA expressions, as well as MAPK and NF-κB activation. To our knowledge, this is the first description of the inhibitory roles for CKRF in TLR4- or TLR9- associated signaling in BMDMs. Collectively, these results demonstrate that CKRF specifically modulates distinct TLR4- and TLR9-mediated inflammatory responses, and further studies are urgently needed for their in vivo roles for potential therapeutic uses, such as in systemic inflammatory syndromes.