인간 유방암 MDA-MB-231 세포에서 Peptide H에 의한 IL-6 발현 억제효과

성대일,박잠언,김한복,Sung, Dae Il,Park, Jameon,Kim, Han Bok 한국미생물학회 2014 미생물학회지 Vol.50 No.3

암, 류마티스, 크론병 등은 만성염증과 관련되어 있다. Interleukin-6 (IL-6)는 염증의 주요 매개인자이다. 청국장은 콩 발효식품으로 대두단백질이 분해되어 다양한 peptide가 생성되면서, 생리활성물질이 될 수 있다. 본 연구에서는 청국장에서 분리한 peptide (Gly-Val-Tyr-Tyr-Met-Tyr)를 가공한 6mer H, [(Glu-Val-Tyr-Tyr-Met-Tyr(EVYYMY)]가 유방암세포 MDA-MB-231에서 IL-6 발현을 억제할 수 있는지 여부를 결정하였다. MDA-MB-231 세포에 peptide H를 처리해 주면, IL-6 발현은 peptide를 처리하지 않은 control에 비해, 크게 억제되었으며, 세포의 성장은 농도의존적으로 억제되었다. 암 이외에, 류마티스, 크론병 등 만성염증 질환에서 IL-6 신호의 차단은 염증개선에 유효한 것으로 알려져 있다. Peptide H는 염증과 관련된 IL-6 발현의 감소효과가 있으므로, IL-6 관련 암, 류마티스, 크론병 등의 치료제 개발로 응용, 연결될 수 있을 것이다. Chronic inflammation is involved in cancers, rheumatoid arthritis, and Crohn's disease. Inerleukin-6 (IL-6) plays major roles in inflammation. Chungkookjang, fermented soybean contains diverse peptides produced by cleavage of soybean proteins. The peptides can be bioactive compounds. Peptide (Gly-Val-Tyr-Tyr-Met-Tyr was purified from Chungkookjang, and modified to be 6mer H, Glu-Val-Tyr-Tyr-Met-Tyr (EVYYMY). Peptide H's activity to suppress IL-6 expression in a human breast cancer cell, MDA-MB-231 was determined. IL-6 Expression was reduced in the cell treated with peptide H 25 times less than controls which were not treated with peptide H. Proliferation of MDA-MB-231 cells was inhibited by peptide H, which is concentration-dependent. Blocking of IL-6 signals is known to be effective in reducing inflammation in rheumatoid arthritis, Crohn's disease, and cancers. Since peptide H can reduce inflammatory IL-6 expression, application of this study will contribute to drug development for diseases which are caused by excessive IL-6.

OMC-2010 추출물이 마우스의 비장세포 cytokine 생성에 미치는 영향

배기상 ( Gi Sang Bae ),박경철 ( Kyoung Chel Park ),최선복 ( Sun Bok Choi ),조일주 ( Il Joo Jo ),서상완 ( Sang Wan Seo ),김종진 ( Jong Jin Kim ),신용국 ( Yong Kook Shin ),김민선 ( Min Sun Kim ),박규환 ( Kyu Hwan Park ),김현식 ( Hyu 대한본초학회 2012 大韓本草學會誌 Vol.27 No.5

Objective : This study was performed to estimate the effects of OMC-2010 extract on cytokine production in mouse spleen cells. Methods : Mouse spleen cells were pre-treated with ethanol and water extract of OMC-2010 for 1 h, then stimulated with lipopolysaccharide (LPS, 1 μg/ml) for 48 h. Then the cells were harvested for real-time reverse transcription polymerase chain reaction to detect cytokines. Results : OMC-2010 ethanol extract significantly inhibited the LPS-induced interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and IL-5 mRNA expressions, but not shown such changes in IL-6, IL-4, IL-13. OMC-2010 water extract significantly inhibited the LPS-induced TNF-alpha, and IL-5 mRNA expressions, but not shown such changes in IL-1beta, IL-6, IL-4, IL-13. Conclusions : Theses results could suggest that both ethanol and water OMC-2010 extract could inhibit the TNF-alpha and IL-5 mRNA expression.

OMC-2010 구성약재 배합추출물 투여가 Ovalbumin으로 유도한 마우스 알레르기성 기관지 천식에 미치는 영향

조일주 ( Il Joo Jo ),배기상 ( Gi Sang Bae ),최선복 ( Sun Bok Choi ),송호준 ( Ho Joon Song ),박성주 ( Sung Joo Park ),서상완 ( Sang Wan Seo ),옥주안 ( Joo An Ok ),김민선 ( Min Sun Kim ),백선종 ( Sun Jong Baek ),배익현 ( Ik Hyun Bae 대한본초학회 2013 大韓本草學會誌 Vol.28 No.5

Objectives: We recently have reported that constituents of OMC-2010 have an immuno-modulatory effects via inhibiting tumor necrosis factor (TNF)-alpha and interleukin (IL)-5. In this study, based on previous data, we investigated the effects of combinations with each OMC constituents on splenocyte cytotoxicity, cytokine productions, and ovalbumin (OVA) induced experimental allergic asthma. Methods: Mouse splenocytes were pre-treated with ethanol extract of constituents of Rehmannia glutinosa (RG), Pinellia ternata (PT), Schisandra chinensis (SC). We made 4 combinations using RG, PT, and SC (A;1:1:1, B;2:1:1, C;1:2:1, D;1:1:2). The cells were pretreated with A, B, C, or D for 1 h, then stimulated with lipopolysaccharide (LPS, 1 ㎍/ml) for 48 h. Then the cells were harvested for real-time reverse transcription polymerase chain reaction to detect cytokine productions. Then using effective combination from RG, PR and SC, we administrated the combination orally, then challenged with OVA to induce asthma. Then we analyzed the airway hyper-reactivity (AHR), lung histology and lung TNF-α and IL-5 mRNA. Results: A. B. C. and D did not showed significant cytotoxicity on splenocytes. Pre-treatment of A inhibited the expression of TNF-α and IL-5 significantly, but not B, C, and D. In experimental asthma, administration of A significantly inhibited the increase of AHR, lung damage, TNF-α and IL-5 expression. Conclusions: Theses results could suggest that inhibitory effects of the ideal combination with RG, PT and SC (1:1:1) could be applied to treatment of asthma and study of asthma mechanisms.

LPS로 유도한 RAW 264.7 세포의 염증반응에서 자초(紫草)의 항염증 효과

최선복 ( Sun Bok Choi ),배기상 ( Gi Sang Bae ),조일주 ( Il Joo Jo ),박경철 ( Kyoung Chel Park ),서승희 ( Seung Hee Seo ),김동구 ( Dong Goo Kim ),신준연 ( Joon Yeon Shin ),곽태신 ( Tae Sin Gwak ),이정현 ( Jung Hyun Lee ),이금산 ( G 대한본초학회 2013 大韓本草學會誌 Vol.28 No.2

Objective: Lithospermum Erythrorhizon (LE) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that LE aqueous extract could show the anti-inflammatory effects in RAW 264.7cells. The purpose of this study was to investigate the anti-inflammatory effect of aqueous extract from LE on lipopolysaccharide (LPS) - induced inflammatory response. Methods: To measure out the cytotoxicity of LE, we performed the MTT assay. To evaluate the anti-inflammatory effects of LE, we examined the inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-a, interleukin, (IL)-1β and (IL)-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-κB) activation by western blot. Results : Aqueous Extract from LE itself did not have any cytotoxic effect in RAW 264.7 cells. Aqueous extract from LE inhibited LPS-induced productions of inflammatory mediators such as NO, PGE2, and pro-inflammatory cytokines including TNF-a, IL-1β and IL-6 in RAW 264.7cells. In addition, LE inhibited the phosphorylation of p38 kinases (p38), c-Jun NH2-terminal kinase (JNK), and NF-κB activation in RAW 264.7 cells. Conclusion : LE down-regulated LPS-induced production of inflammatory mediators through the inhibition of p38, JNK and NF-κB activation. Taken together, these results could provide the evidence for the anti-inflammatory effects of LE. Therefore, LE may be a novel target in the management of inflammation and help to support a potential strategy for prevention and therapy of inflammatory diseases.

가감소속명탕이 Monosodium Iodoacetate로 유발된 골관절염의 초기변화에 미치는 영향

박동수 ( Dong Soo Park ),정수현 ( Su Hyeon Jeong ),김순중 ( Soon Joong Kim ),서일복 ( Il Bok Seo ) 한방재활의학과학회 2011 한방재활의학과학회지 Vol.21 No.4

Objectives: This study was performed to investigate the effects of Gagamsosokmyeong-tang(Jiajianxiaoxuming-tang) on the monosodium iodoacetate(MIA) induced early stage osteoarthritis in rats. Methods: Osteoarthritis was induced by injection of MIA(0.25 mg) into knee joints of rats. Osteoarthritic rats were divided into control(n=8) and treated(n=8) group respectively. Control group was taken distilled water and treated group was taken extracts of Gagamsosokmyeong-tang(Jiajianxiaoxuming-tang) by orally for 20 days. Body weight was measured at 0, 5, 10, 15, 20 days after MIA injection. At the end of experiment, gross and histopathological examination on the articular cartilages of the knee joints were performed. Proteoglycan(PG) content of articular cartilages were analysed by safranine O staining method. The content of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) in synovial fluids were analysed by enzyme-linked immunosorbent assay(ELISA) method. And also cyclooxygenase-2(COX-2), matrix metalloproteinase 3(MMP-3), inducible nitric oxide synthase(iNOS), calpain immunohistochemical examination on the knee joints were performed. Results: PG content in articular cartilages of the treated group was significantly increased compared with control group. Histopathological osteoarthritic score of the treated group was significantly decreased compared with control group. TNF-α content in synovial fluids, expression of iNOS and calpain in synovial membrane of the treated group were significantly decreased compared with control group. But body weight, IL-1β content in synovial fluids, expression of iNOS and MMP-3 of the treated group were not significantly changed compared with control group. Conclusions: On the basis of these results, we conclude that Gagamsosokmyeong-tang(Jiajianxiaoxuming-tang) has anti-arthritic effects on the MIA induced early stage osteoarthritis in rats.

인간유방암 MDA-MB-231세포에서 peptide H에 의한 TNFα 발현 억제

성대일,박잠언,강충경,김한복,Sung, Dae Il,Park, Jameon,Kang, Choong Kyung,Kim, Han Bok 한국미생물학회 2015 미생물학회지 Vol.51 No.3

청국장은 다양한 peptide류를 포함한다. 청국장 유래의 peptide H를 인간유방암 MDA-MB-231 세포에 처리했을 때, $TNF{\alpha}$ 발현은 뚜렷하게 억제되었다. $TNF{\alpha}$에 의해 유도되는 IL6 발현 역시, peptide H에 의해 감소될 수 있음을 시사해 준다. Peptide H구조는 glucocorticoid, dexamethasone과 전혀 유사하지 않아 그들과 다른 기작으로 $TNF{\alpha}$ 발현억제에 작용할 것을 시사해 준다. Peptide H는 $TNF{\alpha}$ 발현 억제 효과가 있으므로 보다 깊이 있는 연구를 바탕으로, 류마티스 관절염, 크론병 등의 치료제로 개발될 수 있기를 기대해 본다. Chungkookjang (fermented soybeans) contains diverse peptides. Human breast cancer MDA-MB-231 cells were treated with peptide H derived from Chungkookjang, and $TNF{\alpha}$ expression in the cells was conspicuously repressed, suggesting peptide H's regulation of IL6 since IL6 is induced by $TNF{\alpha}$. The structure of peptide H was different from those of glucocorticoid and dexamethasone, suggesting different mechanisms of $TNF{\alpha}$ expression suppression. Peptide H which reduces $TNF{\alpha}$ expression can be developed as drugs for cancer, rheumatoid arthritis and Crohn's disease, after more investigation.

Effects of Moxibustion to Zusanli(ST36) on Alteration of Natural Killer Cell Activity in Rats

Choi, Gi Soon,Han, Jae Bok,Park, Joon Ha,Oh, Sang Deog,Lee, Gi Seog,Bae, Hyun Su,Jung, Sung Ki,Cho, Young Wuk,Ahn, Hyun Jong,Min, Byung Il WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2004 東西醫學硏究所 論文集 Vol.2004 No.-

Moxibustion is one of the major healing techniques in Oriental medicine. It has been widely used in many diseases such as rheumatoid arthritis, Hashimoto disease, breech presentation, etc. However, till now, effects of moxibustion on natural killer (NK) cell activity and relations between sympathetic nerve system (SNS) and the immune alteration induced by moxibustion wert not well studied. This study was designed to evaluate effects of moxibustion on NK cell activity and the Intervention of SNS in the alteration of NK cell activity induced by moxibustion. Splenic NK cell cytotoxicity was measured in a standard 4-hour ^(51)Cr release assay. We measured the NK cell cytotoxicity after moxibustion stimulation for 1, 3, 5 and 7 days, and also measured the NK cell cytotoxicity after 3 and 7 days burn stimulation with similar temperature. Interleukin (IL)-2, -4 and interferon (INF)-γ in serum were measured by rat IL-2, -4 and INF-γ ELISA test kit. To evaluate the effects of sympathectomy on alteration of NK cell cytotoxicity, 6-hydroxydopamine (6-OHDA: 50 mg/kg) was used. We showed that NK cell activity of moxibustion stimulation group incrcased at the 3rd day, and declined at the 7th day in comparison with that of the control group. In thc moxibustion stimulation group, NK cell activity was significantly higher than the sham group at the 3rd day. On the contrary, in the burn stimulation group, NK cell activity was significantly higher than that of the sham groups at 3rd and 7th days. INF-γ level after 3 days in the moxibustion stimulation group was significantly higher than that of the sham group. IL-2 Ievel among groups were not different. IL-4 was not detected in serum with this method. Sympathectomy abolished the NK cell activity alteration induced by moxibustion. The results suggest that moxibustion modulates NK cell activity, along with INF-γ, and SNS is mediating these effects.

Jageum-Jung, the herbal pharmaceuticals, inhibits the hepatic fibrogenesis as mediated with TGF-β1/smad signaling

송유림,Jang Mi Hee,Jang Boyun,Bae Su Jin,Bak Seon Been,Lee Sung Min,Yun Un-Jung,Lee Ju Hee,Park Sang Mi,Jung Dae Hwa,Sa Bok Suk,Song Jong Kuk,이은혜,김광연,Park Kwang-Il,김영우,김상찬 대한독성 유전단백체 학회 2022 Molecular & cellular toxicology Vol.18 No.2

Background Herbal prescriptions have various effects and their efficacy is potentiated by the use of combinations of medicinal herbs. Objective Jageum-Jung (JGJ) is a traditional oriental medical prescription composed of five herbs. It has been used for detoxifi cation, and as an anti-inflammatory and antitumor agent. However, the effect of JGJ on hepatic fibrogenesis is unclear. Results We investigated the role of JGJ in TGF-β1/smad signaling, which is implicated in fibrogenesis, and its hepatoprotective effect in CCl 4 -treated mice with liver fi brosis. Treatment of LX-2 cells with TGF-β induced expression of mediators (α-SMA, PAI-1, and MMP-2) of fibrogenesis and activation of proinflammatory cytokines (TNF-α, IL-1β, and IL-6). However, these were downregulated by pretreatment with JGJ. In mice, oral administration of JGJ prevented liver injury induced by CCl 4 , as indicated by decreases in the ALT and AST levels. Conclusions JGJ inhibits hepatic fibrogenesis and TGF-β1/Smad signaling.

토의 수업을 통한 중학교 교과서 소설 지도

박재일,송복승 순천대학교 어학연구소 2001 어학연구 Vol.12 No.-

기니픽에서 Kanamycin 이독성

박찬일,송영복,정봉진,박용호 충남대학교 의과대학 지역사회의학연구소 1999 충남의대잡지 Vol.26 No.2

To evaluate experimental kanamycin - induced ototoxicity, changes of hearing loss were observed after administration of kanamycin in guinea pig, using auditory brainstem rcsponse(ABR) audiometry. Kanamycin(KM), 50mg/kg/day(group I), 100mg/kg/day(group Ⅱ), 200mg/kg/day(group Ⅲ) and 400mg/kg/day(group IV), was injected intramuscularly in each group and ABR thresholds were measured every other days through 50 days after the initial administration of KM. The injection of KM was discontinued at the day when the ABR threshold was increased more than 40 dB in each guinea pig. After the discontinuation of KM injection, ABR thresholds recovered progrssively to the base line level before the day 50 in group I and Il. But the ABR threshold changes were progressed after discontinuation of KM injection and finally they showed no responses in group III and IV. The results suggested that high dose KM administration could result progressive and irreversible hearing loss after the discontinuation of KM administration.