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.

위상피세포에서 Helicobacter pylori 형태 변화가 Interleukin-8 분비에 미치는 영향

이학성,김혜원,홍원선,민영일,정훈용,김해련,양석균,이미화 대한소화기학회 1999 대한소화기학회지 Vol.33 No.6

Background/Aims: Interleukin-8 (IL-8) has been reported to play a critical role in Helicobacter pylori (H. pylori)-associated gastric mucosal damage. H. pylori exist in both bacillary and coccoid forms in the stomach. In contrast to bacillary forms, it is not clear whether coccoid forms stimulate gastric epithelial cells to produce IL-8. This study was conducted to investigate the effects of coccoid forms on IL-8 production. Methods: H. pylori strains of ATCC 43504, ATCC 43526 and three clinical isolates were used in the present study. Coccoid forms were induced by culturing bacillary forms of H. pylori for more than 84 hr. After co-culture of two human gastric adenocarcinoma cel lines (KATO III and AGS) with five strains of H. pylori, the levels of IL-8 were determined in th supernatants by enzyme linked immunosorbent assay. Results: The levels of IL-8 in KATO III and AGS cells were markedly elevated up to 6-9 hr after co-culture with the bacillary forms. The IL-8 levels produced in both cell lines by the coccoid forms were significantly lower than those by the bacillary forms in all strains. Conclusions: These results suggest that coccoid forms are much less implicated in IL-8- mediated gastric mucosal damage than bacillary forms.

인간 복막 중피 세포의 Transforming Growth Factor-β1(TGF-β1) 합성에 관한 연구

한대석,최진희,윤견일,강덕희,임현정,홍영숙 대한신장학회 1999 Kidney Research and Clinical Practice Vol.18 No.3

Objective:to investigate the effect of high glucose and spent peritoneal dialysate on the TGF-β1 synthesis of cultured human peritoneal MC(HPMC); to examine the effect of costimulation with high glucose or dialysate and cytokines, interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α), on transforming growth factor(TGF-β1) synthesis of HPMC. Design:HPMCs were exposed to different concentrations of glucose(30, 60 & 90 mM/L) or spent peritoneal dialysate for 48 hours in the absence or presence of IL-1β(1ng/ml) and TNF-α(1ng/ml). TGF-β1 mRNA expression was assessed by Northern blot analysis and TGF-β1 protein synthesis and release by Western blot analysis with immunoprecipitation. Results:Exposure of MC to high glucose condition(30mM, 60mM & 90mM of D- glucose) induced 2.3-, 3.6- and 4.0-fold increases in TGF-β1 mRNA expression of MC with enhanced TGF-β1 protein synthesis and secretion into the media. Incubation with spent dialysate also significantly increased TGF-β1 mRNA expression & protein pared to control media(P$lt;0.05) Stimulation with IL-1β(1ng/ml) or TNF-α(1ng/ml) significantly increased TGF-β1 mRNA expression after 48 hours above the control level by 2.7-fold and 2.1-fold, respectively. However, TNF-α-induced increase in TGF-β1 mRNA expression was not translated into TGF-β1 protein secretion whereas IL-1β stimulation induced a significant increase in TGF-β1 protein secretion as well as TGF-β1 mRNA expression. Combined stimulation of high glucose or spent dialysate together with IL-1β or TNF-α showed a greater increase in TGF-β1 mRNA expression and protein secretion compared to stimulation with high glucose or spent dialysate alone. Conclusion:Our results clearly show that high glucose concentration of peritoneal dialysate and spent dialysate themselves might be sufficient to stimulate the production of TGF-β1 by peritoneal mesothelial cell. This state of chronic induction of TGF-β1 is further exaggerated in the presence of peritonitis because of stimulatory effect of proinflines, resulting in the augmented TGF-β1 synthesis, thus promoting peritoneal fibrosis.

사람 위선암에서 cathepsin L의 발현증가

홍원선,홍석일,박인철,손영숙,정훈용,양석균,김해련,민영일 울산대학교 의과대학 1996 울산의대학술지 Vol.5 No.1

cathepsin L은 lysosomal cysteine 단백분해효소로서 기저막(basement membrane)과 세포외기질(extracellular matrix)을 파괴하여 암세포의 침윤과 전이에 중요한 역할을 하는 물질로 알려져 있다. 이러한 cathepsin L에 대한 mRNA 발현도를 5개의 사람 위선암(gastric adenocarcinoma) 세포주와 5명의 위선암 환자에서 채취한 조직에서 방사능으로 표지된 cathepsin L특이 cDNA를 사용한 Northern blot법으로 측정하였다. 위암의 전이병소에서 수립한 세포주인 SNU-5, SNU-16, MKN-45와 Kato Ⅲ에서는 cathepsin L mRNA가 발현되었으나 원발병소에서 수립한 AGS 세포주에서는 mRNA의 발현이 관찰되지 않았다. 5명의 위암 환자에서는 원발병소, 전이가 확인된 임파절 및 암 근처 정상 위점막에서 각각 조직을 채취하여 cathepsin L mRNA의 발현을 측정하였다. 원발병소와 전이병소에서는 모두 cathepsin L mRNA가 발현되었으나 정상 위점막조직에서는 전예에서 mRNA 발현이 관찰되지 않았다. 한편 mRNA의 발현도는 1예에서는 전이병소가 원발병소에 비해 높았으나, 2예에서는 전이병소에서 발현도가 낮았으며, 나머지 2예에서는 원발병소와 전이병소 사이에 차이가 없어, 원발병소와 전이병소 사이에 mRNA의 발현도의 일관성 있는 경향은 관찰되지 않았다. 이상의 결과는 cathepsin L은 위암의 발생과 진행에 있어 암세포의 침윤과 전이를 촉진하는 것 이외에 또 다른 역할을 할 가능성을 시사하고 있다고 사료된다. Cathepsin L, a lysosomal cysteine protease, is known to play an important role in cancer invasion and metastasis by degrading the components of basement membrane and extracellular matrix. The mRNA expression of cathepsin L was determined by Northern blot analysis using a radiolabeled cDNA specific for cathepsin L in five human gastric adenocarcinoma cell lines and five surgical specimens of primary gastric adenocarcinomas, their metastatic lymph nodes and matched adjacent normal mucosae. The mRNA of cathepsin L was expressed in all of the four cell lines established from the metastatic sites, SNU-5, SNU-16, MKN-45 and Kato Ⅲ, while not detected in one cell line established from the primary site, AGS. The mRNA was expressed in all of the five primary and five metastatic cancer specimens tested, while it was not detected in all matched normal mucosae. The intensities of the mRNA expressions, however, did not show the consistent pattern between primary sites and metastatic lymph nodes. These results suggest that cathepsin L may have the other function in addition to facilitation of the invasion and metastasis during the development and progression of stomach cancer.

약물치료에 가역적 회복을 보인 갈색세포종에 동반된 확장성 심근증 1례

홍숙경,최현,이승철,천경일,김영철,한재룡,김미숙,정경태,박순창 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.2

구형 Helicobacter pylori의 중성구 매개 산화활성

홍원선,김혜원,이학성,명승재,정훈용,양석균,김진호,민영일,정명희 대한암예방학회 2000 Journal of cancer prevention Vol.5 No.3

완전 생분해성과 광분해성을 갖는 필름에 대한 연구

이상일,서석훈,홍경민,신용섭,장상희,신부영 영남대학교 공업기술연구소 2001 工業技術硏究所論文集 Vol.29 No.1

Bio-and-photodegradable polymer composites were prepared by blending biodegradable aliphatic polyester and photodegradable master batch(M/B). Photodegradability, biodegradability, thermal properties and mechanical properties were investigated. The biodegradability of EnPol(G4600) composites decreased wish increasing the amount of M/B, while that of EnPol(G8000) composites increased. Tensile strength and elongation decreased with increasing the time of outdoor exposure and the amount of M/B but modulus comparatively maintained. The mechenical properties decreased as the content of M/B increased, while the melting temperature unchanged.

三日酒와 三日 基以內로 빚어지는 우리나라의 速成酒 : Ⅱ. 찹쌀로 빚은 速成酒 Ⅱ. About Brewing from Glutinous Rice

錢精日,申敏子,崔榮辰,金賢淑,李惠靜,鄭在洪,白淑殷 동아시아식생활학회 1999 東아시아食生活學會誌 Vol.9 No.3

This study was carried out to understand the brewing and processing methods of rapid-brew alcoholic beverage. In the contents of 45 classical records, there were 68 items about rapid-brew alcoholic beverage and single and double brew alcoholic beverage. Those alcoholic beverage of 68 items above, were made from green grown at that time-rice, glutinous rice, regular rice. Selected 38 items among those brewages, alcoholics from glutinous rice, were distributed into 4 patterns. Four patterns, grounded on rapid-brewing and processing methods, were set one thing to another and analyzed.

콩의 개화기 전후 공급과 수용부위의 생장반응과 수량에 대한 질소의 효과

박재홍,송범헌,이철원,손석용,김홍식,박상일 忠北大學校 農業科學硏究所 2002 農業科學硏究 Vol.19 No.-

This study was conducted to examine the nitrogen effects on the growth responses, the nodulation, and the distribution of dry weight of plant tissues at major growth stages before and after the flowering stage, and to evaluate the yield components and yields with different nitrogen levels. Hwangkeum cultivar(Glycine max L mereill) was cultivated under five different nitrogen levels, 0, 2, 4, 6, 8, N Kg/10a. Stem length and branching number, which were investigated with different N levels at major growth stages, were rapidly increased for 14days for before and after the flowering stage compared to the other growth stages. They were clearly higher with treatment of 2 and 4 N kg/10a than those of other N treatments. Pod number was slightly increased from the flowering to beginning maturity. It was the highest in the treatment of 2 N Kg/10a. Comparing grain number per pod with different N levels, two grains per pod was much higher in all N treatments except for the treatment of 6 N Kg/10a. Dry weight of shoot(including leaf, stem, and pod) was rapidly increased from the flowering stage to the full seed stage and then gradually increased after the full seed stage, whereas the dry weight of root(including the nodule and root) was rapidly increased until to full pod stage and then linearly decreased from the full pod stage until the beginning maturity stage. Comparing dry weight with different N levels, the dry weight of shoot was the highest in the treatment of 4 N Kg/10a, while it of root was the highest in the treatment of 2N Kg/10a. The dry weight of nodule was the highest, 13.1 Kg/10a, at full pod stage. Comparing the dry weight of nodule with different N levels, it was increased to the application amount of 4 N Kg/10a and then clearly decreased with more application amount of N than 4 Kg/10a. The yield components which were mostly affected to the yield were pod number per plant and grain number per plant. They were 57.5 and 106.1, respectively, with treatment of 4 N Kg/10a, which showed the highest yield, about 266 Kg/10a. Comparing yield index with different N levels to the control, the yields with treatment of 2 and 4 Kg/10a were increased to 21% and 34%, respectively.

기능성 생식, 다이어트식 및 장개선제가 비만개선에 미치는 영향

전태일,전은자,김창성,이주용,안홍석,임병우,최영숙,박웅채,박동기 建國大學校附設農業資源開發硏究所 2001 農資源開發論集 Vol.23 No.-

Obesity is defined as an excess of body fat and is closely related to diabetes, hypertension and heart disease. Dietary cure has been paid attention as a method for preventing from or curing obesity. The effect of some food products developed in this laboratory, such as, functional saengsik (Health & Joy saengsik), diet food (Health & Joy diet meal) and intestine function activator (Cell-pa, commercial name) on curing and protecting from obesity were investigated. Diet program was applied to 31 adults (Males 22, Females 9) with above 120% body mass index (BMI). After diet program was applied, body weight, body fat and fat weight decreased by 1, 4.8 and 4.5% (p<0.01), HDL-cholesterol increased by 3.6% and LDL-cholesterol and atherogenic index decreased by 6.6 and 7.7% (p<0.05). Consequently, the food products developed in this laboratory effectively reduced the obesity.