담배 니코틴에 의한 사람 태아 성상세포에서 종양괴사인자(TNF-α)의 발현 억제작용

손일홍,이성익,양현덕,한선정,석승한,이재규,김재현,박주영,문형인,이성수,Son, Il-Hong,Lee, Sung-Ik,Yang, Hyun-Duk,Han, Sun-Jung,Suk, Seung-Han,Lee, Jai-Kyoo,Kim, Jae-Hyun,Park, Joo-Young,Moon, Hyung-In,Lee, Sung-Soo 대한화학회 2007 대한화학회지 Vol.51 No.3

니코틴은 사람 대식세포에서 interleukin 2 (IL-2)와 종양괴사인자 (tumor necrosis factor-alpha; TNF-α) 가 생성되는 것을 억제하는데, 이러한 억제작용은 cytokine 유전자 발현 중 전사단계에서 전사인자의 활성을 억제함으로써 일어난다. 이러한 니코틴의 면역반응 억제작용은 아프타성궤양 및 궤양성대장염, 알레르기성폐 포염, 건초열 등에서도 보고되고 있다. 만일 중추신경계에서도 위와 같은 니코틴의 면역억제 작용이 일어난 다면 다발성경화증과 같은 면역반응 매개질환의 치료에 새로운 전기가 마련될 수 있을 것이다. 본 연구에서 는 중추신경계의 여러 면역반응 매개질환의 병태생리에 대한 이해를 넓히고자, 이미 알려진 니코틴의 cytokine 생성억제가 사람 중추신경계의 성상세포에서도 일어남을 확인하고 그 억제기전을 밝히고자 하였다. 이를 위 하여 사람 태아 성상세포에 다양한 농도의 니코틴과 IL-1β를 처리한 다음 TNF-α mRNA의 발현 정도와 NF- κB의 활성을 비교, 분석하여 다음과 같은 결과를 얻었다. 1. 사람 태아 성상세포를 0.1-20 μg/ml의 니코틴으로 처리해 본 결과 10 μg/ml 이상의 농도에서 세포독성능이 나타나기 시작하였다. 2. 사람 태아 성상세포에 IL- 1β를 처리하면 2시간만에 TNF-α mRNA가 최대로 발현되었으며 그 이후로는 점진적으로 감소하였다. 3. 사 람 태아 성상세포를 1 및 0.1 μg/ml의 니코틴으로 전처리한 후 IL-1β로 자극한 군에서는 IL-1β 단독 처리군에 비해 TNF-α mRNA의 발현이 감소하는 양상을 보였다. 1 μg/ml의 니코틴을 처리한 경우에는 8시간 이후부터 TNF-α mRNA의 발현이 현저하게 감소하여 12시간에 최대로 감소하였다. 또한 0.1 μg/ml의 니코틴을 처리한 군에서는 24시간에 가장 현저하게 감소하였다. 4. 성상세포에 IL-1β로 처리한 군에서는 강력한 NF-κB의 활성 을 확인할 수 있었으며, 니코틴을 전처리하고 IL-1β 자극한 군에서는 NF-B의 활성이 감소하였다. 결론적으로 일정농도 이상의 니코틴은 세포독성효과를 나타내나 적정한 농도와 시간 경과후 니코틴은 사람 태아 성상세포에서 IL-1β에 의해 유도되는 TNF-α의 발현 감소를 유도하며, 이는 NF-κB의 활성을 감소시킴으로써 나타난다고 생각된다. The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

Early Phase of UVB - induced GM - CSF Upregulation in Epithelial Cell Line is not Totally Dependent on IL - 1α

Park, Kyoung Chan,Kim, Kyu Han,Ahn, Jong Seong,Chung, Jin Ho,Youn, Jai Il,Whang, Ji Hwan,Youn, Sang Woong,Kim, Young Gull,Koh, Woo Seok,Jung, Hyun Chae 대한피부과학회 1997 Annals of Dermatology Vol.9 No.4

Backgrounds : It was demonstrated that ultraviolet(UV) B light induces the release of IL-la in cultured human epithelial cell line and augmentation of GM-CSF production by UVB is reported to be mediated by IL-1α in the murine keratinocyte cell line Pam 212. Objective : The purpose of this study was to evaluate the effects of UVB on kinetic profile of IL-1 and GM-CSF mRNA expression and to see whether synthesis of GM-CSF by UVB can be completely inhibited by blocking IL-1α mediated pathway. Method : We used a competitive RT-PCR for measuring cytokine gene expression in epithelial cell line after UV radiation. Results : The IL-1α mRNA increased as early as 1h after UV irradiation, and then decreased at 3h after the irradiation. Thereafter, the response of IL-1α mRNA was upregulated with a second peak at 6h after the UV irradiation. However, mRNA for GM-CSF increased at 1h after UV light exposure and anti-IL-1α antibodies could only partially inhibit UV-augmented GMCSF production. Conclusion : UVB induced GM-CSF production seemed to be mainly mediated by UVB induced IL-1α but these results suggest that UVB may also induce GM-CSF production through an IL-1α independent pathway.

Interleukin-4와 히스타민이 알레르기성 비염과 비 알레르기성 비염에서 비점막 섬유아세포에 미치는 영향

김성완,조중생,박재경,차창일,김광일 대한이비인후과학회 1999 대한이비인후과학회지 두경부외과학 Vol.42 No.3

Nicotine Suppresses TNF-${\alpha}$ Expression in Human Fetal Astrocyte through the Modulation of Nuclear Factor-${\kappa}B$ Activation

Son, Il-Hong,Park, Yong-Hoon,Yang, Hyun-Duk,Lee, Sung-Ik,Han, Sun-Jung,Lee, Jai-Kyoo,Ha, Dae-Ho,Kang, Hyung-Won,Park, Joo-Young,Lee, Sung-Soo The Korean Society of Toxicogenomics and Toxicopro 2008 Molecular & cellular toxicology Vol.4 No.2

Parkinson's disease (PD) progresses severely by a gradual loss of dopaminergic neurons in the substantia nigra (SN). Epidemiological studies showed that the incidences of PD were reduced by smoking of which the major component, nicotine might be neuroprotective. But the function of nicotine, which might suppress the incidences of PD, is still unknown. Fortunately, recently it was reported that a glial reaction and inflammatory processes might participate in a selective loss of dopaminergic neurons in the SN. The levels of tumour necrosis factor (TNF)-${\alpha}$ synthesised by astrocytes and microglia are elevated in striatum and cerebrospinal fluid (CSF) in PD. TNF-${\alpha}$ kills the cultured dopaminergic neurons through the apoptosis mechanism. TNF-${\alpha}$ release from glial cells may mediate progression of nigral degeneration in PD. Nicotine pretreatment considerably decreases microglial activation with significant reduction of TNF-${\alpha}$ mRNA expression and TNF-${\alpha}$ release induced by lipopholysaccharide (LPS) stimulation. Thus, this study was intended to explore the role of nicotine pretreatment to inhibit the expressions of TNF-${\alpha}$ mRNA in human fetal astrocytes (HFA) stimulated with IL-$1{\beta}$. The results are as follows: HFA were pretreated with 0.1, 1, and $10{\mu}g/mL$ of nicotine and then stimulated with IL-$1{\beta}$ (100 pg/mL) for 2h. The inhibitory effect of nicotine on expressions of TNF-${\alpha}$ mRNA in HFA with pretreated $0.1{\mu}g/mL$ of nicotine was first noted at 8hr, and the inhibitory effect was maximal at 12 h. The inhibitory effect at $1{\mu}g/mL$ of nicotine was inhibited maximal at 24 h. Cytotoxic effects of nicotine were noted above $10{\mu}g/mL$ of nicotine. Moreover, Nicotine at 0.1, 1 and $10{\mu}g/mL$concentrations significantly inhibited IL-$1{\beta}$-induced TF-${\kappa}B$ activation. Collectively, these results indicate that in activated HFA, nicotine may inhibit the expression of TNF-${\alpha}$ mRNA through the pathway which suppresses the NF-${\kappa}B$ activation. This study suggests that nicotine might be neuroprotective to dopaminergic neurons in the SN and reduce the incidences of PD.

Poster Session : PS 0694 ; Rheumatology ; Appearance of Psoriasis after TNF-a Blocker and Use of Ustekinumab or Tocilizumab for Refractory Monoarthritis

( Jin Young Moon ),( Dong Jin Go ),( Jae Hyun Lee ),( Jin Kyun Park ),( Eun Bong Lee ),( Yeong Wook Song ),( Jai Il Youn ),( Eun Young Lee ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Nowadays, tumor necrosis factor-a (TNF-a) blockers are used for the treatment of RA, infi ammatory bowel diseases (IBD), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis. Paradoxically, there are some reports of appearance of psoriasis after TNF-a blockers. We report a patient who have seronegative mono-rheumatoid arthritis (mono-RA) on knee joint that experienced psoriasis after TNF-a blocker therapy (adalimumab and etanercept). For the patient, oral medication is not available due to intolerance; thus, we tried ustekinumab which is an anti-IL-12/23 monoclonal antibody that has been used to treat psoriasis. After ustekinumab injection, psoriatic skin lesions and joint symptoms were much improved in the patient. But in the following period, joint pain and swelling aggravated and synovial fi uid cytokine levels such as IL-6 and IL-17 were elevated. Treatment was changed to tocilizumab, humanized monoclonal antibody against IL-6 receptor. After injection, knee joint swelling rapidly subsided without worsening of psoriatic skin lesion.

Case Reports : Appearance of Psoriasis after Tumor Necrosis Factor-α Blocker and Use of Ustekinumab or Tocilizumab for Refractory Monoarthritis

( Jinyoung Moon ),( Nakwon Kwak ),( Jin Lim ),( Dong Jin Go ),( Jae Hyun Lee ),( Jin Kyun Park ),( Eun Bong Lee ),( Yeong Wook Song ),( Jai Il Youn ),( Eun Young Lee ) 대한류마티스학회 2015 대한류마티스학회지 Vol.22 No.4

Nowadays, tumor necrosis factor-α (TNF-α) blockers are used for treatment of rheumatoid arthritis, inflammatory bowel diseases, ankylosing spondylitis, psoriatic arthritis, and psoriasis. Paradoxically, there are some reports on the appearance of psoriasis after administration of TNF-α blockers. Here, we report on a patient with monoarthritis in a knee joint who experienced psoriasis after TNF-α blocker therapy (adalimumab and etanercept). Oral medication was not a treatment option due to patient intolerance; thus, we tried ustekinumab, an anti-interleukin (IL)-12/23 monoclonal antibody used for treatment of psoriasis. Following ustekinumab injection, psoriatic skin lesions and joint symptoms were much improved. However, in the following period, joint pain and swelling became aggravated and synovial fluid cytokine levels including IL-6 and IL-17 were elevated. The treatment was changed to tocilizumab, a humanized monoclonal antibody against IL-6 receptor. After injection, knee joint swelling rapidly subsided without worsening of psoriatic skin lesions. (J Rheum Dis 2015;22:263-268)

조갑진균증에서 Ciclopirox Nail Lacquer의 치료효과

박경찬,김정애,방형돈,조광현,윤재일,김병수 대한감염학회 1995 감염 Vol.27 No.3

배경 및 목적:조갑진균증의 치료에 있어 국소용 항진균제는 조갑판을 통과하지 못하기 때문에 치료율이 낮은 것으로 알려졌으나 최근 조갑판을 통과하여 조상에서도 높은 치료농도를 유지할 수 있는 국소용 항진균제인 ciclopirox nail lacquer가 개발되었다. 이에 본 저자들은 8% ciclopirox nail lacquer 단독 도포의 조갑진균증에서의 치료 효과와 안전성을 알아 보기 위한 연구를 수행하였다. 방법:표적 조갑판의 감염된 면적의 비율이 50%이하인 경증의 조갑진균증 환자 27명을 평가 대상으로 하였으며 8% ciclopirox nail lacquer 1일 1회 도포요법으로 6개월간 치료하였다. 매 방문시마다 감염면적 비율을 기록하였고 치료 전과 치료 후 진균 검사를 시행하였다. 결과: 1)표적조갑판의 감염 면적이 치료 전 평균 28.9%에서 치료 종료시 4.7%로 통계적으로 유의하게 감소하였다(p<0.001). 2)KOH 직접 도말 검사와 진균 배양 검사에서 모두 음성인 진균학적 완치율은 치료 종료시 77.8%였다. 3)부작용으로는 3명(11.1%)에서 일시적 작열감, 조갑 감입 등을 호소하였다. 결론:경증의 조갑진균증 치료에 있어 8% ciclopirox nail lacquer는 비교적 좋은 치료 효과를 보이며 부작용이 적은 약제로 생각된다. Background: Topical antifungal agents have been ineffective in the treatment of onychomycosis because they could not reach the infected nail bed. 8% ciclopirox nail lacquer is a new topical antimycotic which is characterized by excellent penetration into the nail plate. We performed a study to assess the therapeutic efficacy and safety of 8% ciclopirox nail lacquer in the treatment of onychomycosis. Methods: We assessed 27 onychomycotic patients whose affected area of target nail plate was not more than 50%. The patients were instructed to apply 8% ciclopirox nail lacquer once daily and evaluated monthly for 6 months. Mycological examinations were done before and after the treatment. Overall efficacy, tolerability, cosmetic acceptance and adverse effects were assessed at the end of 6 months' treatment. Results: The mean percentage of affected area decreased from 28.9% to 4.7%. Mycological cure rate was 77.8% at the end of the treatment. Overall efficacy assessed by physician and patients were similar and evaluated as complete cure in 48% and 44%, respectively. Tolerability and cosmetic acceptance were excellent or good in most of the patients. No systemic adverse effects were found, but 3 patients complained of mild prickling sensation or ingrowing toe nail. Conclusions: These data suggest that 8% ciclopirox nail lacquer is safe and effective in the treatment of mild onychomycosis.

푸드뱅크 기탁식품의 안전성 확보를 위한 HACCP 제도 적용

김철재,박현신,배현주,이지해,양일선,강혜승 한국식생활문화학회 2002 韓國食生活文化學會誌 Vol.17 No.3

The purpose of this study was to analyze the problems arising from the actual conditions of the Foodbank, and to implement the HACCP system as a solution in terms of increasing the safety of donated food within the Foodbank. In order to apply HACCP system, the entire Foodbank working process such as preparation, collection, transportation, division, and distribution was considered and analyzed to decide the application point for CCPs. Donated foods mainly consisted of processed foods, raw materials, lunch boxes, and cooked foods from mass catering establishments, which dominated over the others in terms of quantity. Cooked foods were divided into three groups based on menu-types and processing methods. Temperature, pH, and aw were measured on cooked foods, and Total Plate Count, Coliforms, E. coli, Salmonella spp., Staphylococcus aureus, Listeria monocytogenes, and E. coli O157:H7 were conducted in order to apply a HACCP plan. Form these experiments, temperature, pH, and aw of donated food were likely contributed to microbial growth. Donated foods before HACCP implementation showed high numbers in terms of total plate count and Coliforms, both well over the acceptable standard levels. By setting the CCPs on maintenance of donated food below 10℃ and using a 75 ℃ reheating method, microbiological hazard levels were able to be controlled and lowered. From these results, it is concluded that in order to guarantee food safety, foods donated to the Foodbank must not only maintain a reasonable level of initial microbiological growth, but also must be handled properly through time and temperature controls within the Foodbank system. Furthermore, in terms of implementing the HACCP plan within the Foodbank management structure, basic food safety and sanitation measures, such as reheating facilities and various cold chain systmes such as refrigerated vehicle for food transportation are importantly needed. The training and education of Foodbank personnel and management in areas such as awareness of hygiene and safe food handling and practice are also required and necessary.

21세기를 향한 국민 생활체육의 과제

서재균,김승일,윤우상,박영진,곽은창 경희대학교 사회체육연구소 1996 體育科學論叢 Vol.- No.9

The purpose of the present study was to investigate the participation patterns of middle aged subjects, and to make suggestions for the promotion of the sport-for-all movement in Korea. The results of a questionnaire answered by 2125 middle aged male and female subjects were compared between sexes, age groups and educational back-ground using SAS computer program. The conclusions of this study were as follow: 1. Most subjects answered that they had very limited leisure time during week days and week ends. 2. It was shown that most middle aged subjects preferred to rest instead of participate in sport activities during their leisure time. 3. The intensity and frequency of sport activity were too low to improve cardio-vascular endurance. 4. To improved the availability of sport facilities, better management was recommanded.

폴리머 콘크리트 복합체를 이용한 교통안전 시설물 개발

이명호,이재철,이승우,서장일,박세희 강원대학교 부설 석재복합신소재 제품연구센터 2004 석재연 논문집 Vol.9 No.-

폴리머 콘크리트 복합체를 이용하여 악천후에도 시인성이 좋고 주위의 경관과 어울리는 자동점멸 표지병을 개발하였다. 아날로그 회로에 비해 설계상의 난해한 점이 있으나 상대적으로 간편한 디지털 회로를 사용하여 자동점멸 회로를 구성하였으며, 작업의 능률을 높이고 개발비를 줄이기 위하여 OrCAD를 사용한 Simulation을 실시후 회로를 구성하였다. 표지병의 시공시와 같은 환경에서의 실험에서는 디지털회로의 작은 전류와 표지병간의 거리, 전선의 저항으로 인하여 클럭 및 클리어 신호에 전압강하와 상승/하강 시간의 증가가 나타났다. 표지병은 전자회로와 함께 설치되어야 하므로 방수성을 고려하여 표지병과 전자회로를 일체형으로 설계하였다. 실제 시공시의 환경에서 시행한 실험에서 나타난 문제점을 검토하였으며, 향후 연구방향에 관하여 고찰하였다. Using polymer concrete composite, the automatic-on/off road marker that is well distinguished in a bad weather condition of rainy or foggy day and is well harmonized with. Digital circuit that is hard to design but simpler than an analog circuit is used in designing the automatic-on/off circuit, and it order to raise the working efficiency and lower the development cost, OrCAD, a simulation tool of electric circuit, was used in simulating the circuit. In an experiment conducted under the circumstance of practical application, voltage drop and raising/lowering time increment in the clock and the clear signals are occurred because of small current of digital circuit and resistance of electrical line. Because that the road marker is assembled with the digital circuit, it is designed as one assembled unit by considering water proof. Some problems occurred in the experiment and the future work are discussed.