A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130

Hong, Soon-Sun,Choi, Jung Ho,Lee, Sung Yoon,Park, Yeon-Hwa,Park, Kyung-Yeon,Lee, Joo Young,Kim, Juyoung,Gajulapati, Veeraswamy,Goo, Ja-Il,Singh, Sarbjit,Lee, Kyeong,Kim, Young-Kook,Im, So Hee,Ahn, Sun The American Association of Immunologists, Inc. 2015 JOURNAL OF IMMUNOLOGY Vol.195 No.1

<P>IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identified-LMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6-stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6-dependent TF-1 cell proliferation. LMT-28 antagonized IL-6-induced TNF-alpha production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6R alpha, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6R alpha complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130.</P>

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.

Immuno-modulatory activity of hot water extracts isolated from Protaetia brevitarsis seulensis larvae following treatment with Bacillus velezensis TJS119

Kook-Il Han,Jeong Tae Kim,Young Ho Nam,Jum Oc Jung,Eunsun Kim,Mi-Hwa Lee 한국응용곤충학회 2023 한국응용곤충학회 학술대회논문집 Vol.2023 No.10

Protaetia brevitarsis seulensis larvae from industrial insects are traditionally recognized as functional health foods in South Korea. We evaluated the immuno-modulatory effects of feeding beneficial microorganism (Bacillus velezensis TJS119) to P. brevitarsis larvae as a dietary source. In this study, we investigated the immune-enhancing activities of P. brevitarsis larvae hot-water extract (PLW) and PLW after treatment with B. velezensis TJS119 (PLWB) using the RAW 264.7 macrophage cell line. We examined the effects of PLWB on cell proliferation, cytokine production, and nitric oxide production in RAW264.7 cells. PLWB showed no cytotoxicity at concentrations ranging from 7.8 to 1,000 μg/mL in RAW264.7 cells. Treatment with PLWB increased the production of nitric oxide and pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)] at doses of 62.5 to 1,000 μ g/mL in RAW264.7 cells. As a result, PLWB exhibited a stronger immune-enhancing effect compared to PLW. In conclusion, the results of this study offer experimental evidence to support the potential utilization of PLWB as an immunity-enhancing nutraceutical ingredient.

Streptococcus dysgalactiae로부터 분리된 히알루론산과 황화된 유도체의 구조와 항염증 활성

홍창일(Chang-Il Hong),정의길(Eui-Gil Jung),한국일(Kook-Il Han),김용현(Yong Hyun Kim),이성희(Sung Hee Lee),이홍섭(Hong Sub Lee),한만덕(Man-Deuk Han) 한국생명과학회 2016 생명과학회지 Vol.26 No.5

히알루론산(HA, Hyaluronic acid)은 β-1, 3-N-acetyl glucosamine과 β-1, 4-glucuronic acid가 반복된 선형 폴리머 고분자로서 생물학적 활성 및 생체친화성 특성 때문에 의약 및 약학분야에서 중요한 분자로 여겨지고 있다. 본 연구는 HA을 S. dysgalactiae으로 얻고, 화학적 방법을 통해 황화된 히알루론산(S-HA, Sulfated hyaluronic acid)유도체를 합성하여 그 구조와 항염증 활성을 비교하였다. HA의 생산은 S. dysgalactiae를 5 l 생물반응기를 이용하여 대량 배양하여 수용성 히알루론산(HA-WS, water soluble hyaluronic acid)과 비수용성 히알루론산(HA-WI, water insoluble hyaluronic acid)을 분리 정제하였다. 특히 HA-WI를 황화시켜 황화된 히알루론산(S-HA) 유도체를 합성하였으며, 그 수율은 90%로 나타났다. 합성된 S-HA의 구조를 FT-IR 및 ¹H/<SUP>13</SUP>C-NMR를 통해 S. dysgalactiae 로부터 생산된 표준 HA, HA-WS 및 HA-WI와 비교 분석한 결과, 황으로 치환된 양상을 확인하였다. 또한, S-HA의 항염증 활성을 RAW 264.7 대식세포를 통해 확인한 결과, S-HA는 천연 형태의 HA (HA, HA-WS)보다 nitric oxide (NO)와 COX-2 및 PGE₂ 유전자 발현이 유의하게 낮게 발현되었다. 염증 매개 cytokine인 TNF-α (<80 pg/ml) 및 IL-6 (<100 pg/ml)의 생성도 S-HA가 천연 HA보다 낮은 수준으로 정량되었다. 이 같은 결과에서 황화된 S-HA은 천연 히알루론산보다 용해성이 우수하고 염증관련 사이토카인의 생성 억제를 통해 항염증 효과를 나타내므로 염증치료제, 성형 및 생체 적용 약물전달 소재로 그 활용이 기대된다. Hyaluronic acid (HA) is an important macromolecule in medical and pharmaceutical fields. HA is a natural and linear polymer composed of repeating disaccharide units of β-1, 3-N-acetyl glucosamine and β-1, 4-glucuronic acid. This work aimed to confirm the structural characteristics and anti-inflammatory activities of HA and its chemically sulfated-HA. HA was produced from a fed-batch fermentation process using Streptococcus dysgalactiae in a 5 l bioreactor. HA was isolated water-soluble form (HA-WS) and water-insoluble form (HA-WI) from culture medium, and was obtained chemically sulfated-derivative (S-HA) that resulted in a 90% yield from HA-WI. The structural features of the sulfated- HA (S-HA) were investigated by FT-IR and ¹H-NMR spectroscopy. The FT-IR and NMR patterns revealed the similarity in both the FTIR spectrum as well as NMR spectrum of both reference standard and purified HA from S. dysgalactiae. The anti-inflammatory activities of HA and S-HA were examined on LPS-induced RAW 264.7 cells. S-HA was significantly inhibited production of pro-inflammatory mediators such as nitric oxide (NO) and PGE₂ and the gene levels of iNOS and COX-2, which are responsible for the production of NO and PGE₂, respectively. Furthermore, S-HA also suppressed the overproduction of pro-inflammatory cytokine TNF-α (<80 pg/ml) and IL-6 (<100 pg/ml) compared to that of HA-WI. The present study clearly demonstrates that HA-S exhibits anti-inflammatory activities in RAW 264.7 macrophage cells.

Interleukin-2와 결핵균 30 kDa 항원이 구개편도 및 말초혈액 T 세포 증식에 미치는 상승효과

박정규,박찬권,조은경,김화중,백태현,고필준,김병국,남부현,나기상,박찬일 충남대학교 의과대학 지역사회의학연구소 1995 충남의대잡지 Vol.22 No.1

Widespread use of BCG has not controlled tuberculosis, and more effective vaccines are clearly needed. Although chemotherapy will remain the mainstay of antituberculosis treatment, the use of adjunctive immunotherapeutic modalitites is attractive, particularly in persons with drug-resistant tuberculosis. Administration of IL-2 or IFN-γto tuberculosis patients enhance bacillary elimination. Cell-mediated immunity is the critical protective immune response in tuberculosis. Mycobacterial antigens are recognized by T cells and that elicit production of protective cytokines are potentially important vaccine antigens. The 30 kDa antigen is secreted in large quantities by growing mycobacteria. That antigen elicits greater proliferation in lymphocytes from healthy tuberculin reactors than healthy tuberculin nonreactors. In this study, the T lymphocyte proliferative responses to 30 kDa antigen from Mycobactrium tuberculosis H37Rv were examined by using tonsilar and peripheral blood lymphocytes from PPD(+) and PPD(-) tonsilectomized persons. When cultured with 30 kD antigen, tonsilar mononuclear leukocytes and T cells of PPD(+) demonstrated more ^3H-thymidine incorporation than PPD(-) persons (stimulation index was 2.5 and 1.9, 0.8 and 1.0, repectively). Peripheral blood mononuclear cells (PBMC) and peripheral blood T lymphocytes were shown the similar responses to this antigen. The combination of IL-2 and 30 kDa antigen elicited a significant proliferative responsiveness in tonsilar mononuclear leukocytes and T cells of PPD(+) persons (SI was 20 and 14.1). PBMC and peripheral blood T cells of PPD(+) persons were also shown a significant responsiveness, but PPD(-) persons did not show. These results demonstrate that the 30 kDa antigen and IL-2 have a synergistic stimulatory property in mycobacteria sensitizing lymphocytes.

SS400강 용접부의 파괴인성치에 관한 연구

국정한,송일규,김봉중,오세용,성호현 한국기술교육대학교 1999 論文集 Vol.6 No.1

In this work, we studied the mechanical properties, structure and the stress intensity factor of the welded areas which were annealed from 500。C to 900。C with an interval of 100。C. The main results are as follow. 1. The as-welded specimen showed the highest tensile strength and yield point. The tensile strength and the yield point decrease as the annealing temperature increased from 500。C to 900。C, and they became smaller in the order of deposited metal, heat affected zone and base metal. 2. The hardness was maximum at about 9 mm from the welding center line, and it decreased drastically in the heat affected zone located between 9∼15mm from the center line. 3. The elongation decreased in the order of base metal, the fusion zone and heat affected zone while it increased as annealing temperature increased. 4. The stress intensity factor(S. I. F.) declined as the length of notch increased and it became smaller in the order of fusion zone, base metal and heat affected zone. This is because fracture toughness is affected by brittlization at heat affected zone as well as the initiation and propagation of cracks.

이종재료 접합부 선단의 크랙 전파 거동

국정한,성호현,송일규 한국기술교육대학교 1997 論文集 Vol.4 No.1

In this study, the crack behavior around the bonded dissimilar materials is analyzed by using by Finite Element Method(FEM) in case that it approaches or passes through the bonded line perpendicularly. The analysis criterion is based on the energy(△U) when the crack progresses or passes through the bonded line. The variables are the width of dissimilar material and distance from the crack tip to the bonded line. Values of E(Young's modulus), V(Poisson's ratio) and △U(Energy) for base material are different from those(E', V', △U') for dissimilar material. The outcome of this study is obtained by comparing △U with △U'

SK 목장 원유의 유질 개선 시범연구

강국희,전태욱,정충일 성균관대학교 생명과학자원연구소 1996 生命資源科學硏究 Vol.3 No.1

A case study was conducted on decrease of bacteria and somatic cell count in the raw milk for the raw milk quality improvement. This study was carried on SK dairy farm in Suwon city that had 4 dairy milking cows. The experiment was tested on 2 cows each for control group and treatment group respectively. Criteria of evaluation on raw milk quality were number of total bacteria, Psychrotrophic bacteria, thermophilic bacteria, coli group and somatic cells. All the cows were applied the same feeding system for 86 days (Mar, 14∼Jane, 7) The results obtained were as follows : Milk contents were fat 3.1%∼4.19% for control group and 3.21%∼4.76% for treatment group; protein 2.65%∼4% for control and 3.04%∼4.37% for treatment; carbohydrate 4.09%∼4.86% for control and 4%∼4.94% for treatment. SNF 7.78%∼9.45% for control and 8.05%∼9.7% for treatment. There was no significant difference in milk contents between control group and treatment. The number of total bacteria was about 8.0×10 exp(5)/ml for control group and 1.0 × 10 exp(5)/ml for treatment group. Psychorotophic bacteria were distributed from 1.79 × l0P/ml to 9.55×10 exp(5) /ml for control group and 5.4×10 exp(3)/ml to 8.95×10 exp(5)/ml for treatment group. Thermophilic bacteria indicated from 6.0×10 exp(3)/ml to 8.95×10 exp(5)/ml for control group, and 5.5×10 exp(2)/ml to 1.1×10 exp(4)/ml for treatment group. The coli group indicated about from 1.6×10 exp(3)/ml to 2.3×10 exp(4)/ml for control group and 1.0×10 exp(2)/ml to 2.9×10 exp(4)/ml for treatment group. The number of somatic cells were 1,534,000(±234,012) for cow No. 2; 197,000 (±59,681) for cow No. 4; 4,240,000 (±1,094,459) for cow No. 9; 951,000 (±784,990) for cow No. 13 respectivley during the experiment period. The somatic cell count did not decrease by the sanitary handling on cows and the tools during experiment period.

열형광체의 발광특성에 관한 연구

김영국,김일홍 慶南大學校 附設 基礎科學硏究所 2002 硏究論文集 Vol.16 No.-

K_2SO_4를 모체로 하여 활성제로 란탄계 원소인 La, Dy, Nd를 첨가하여 800℃와 1100℃의 Ar 분위기의 전기로에서 소성하여 분말형태로 만들었다. K_2SO_4 : La, Dy, Tm, Nd 열형광체의 최대 열형광 강도는 1∼5 wt.%로 변화시켜 첨가했을 때 163℃∼205℃에서 나타났으며, 활성화 에너지는 1.16 eV ∼ 2.72 eV로 나타났다. K_2SO_4 열형광체는 열형광 물질 중에서 X-선에 대한 감응도가 좋았으며, 조사량에 대하여 선형적으로 열형광강도가 증가하였다. 본 연구 결과로 K_2SO_4 열형광체는 저에너지 방사선에 대한 선량계로의 특성이 대체로 양호하므로 열형광선량계로서의 응용이 가능하다. The K_2SO_4 : La, Dy, Tm, Nd thermoluminescent phosphors have been prepared by sintering K_2SO_4 after doping the lantanum elements La, Dy, and Nd at 800℃, 1100℃ for 2 hours in argon atmosphere. The maximum peak of the K_2SO_4 : La, Dy, Tm, Nd glow curves are found at the 163℃∼205℃ when La, Dy, Tm and Nd concentrations are 1 to 5 wt.%. The estimated activation energies are 1.16 eV ∼ 2.72 eV. The K_2SO_4 TL phosphors are the more sensitive X-ray among the TL materials. The dose responses of TL phosphors are linear up to intensity of X-rays. The TL phosphors prepared in this experiment may be utilized to the radiation sensor elements because of their high sensitivity to low energy radiation.

原乳의 세균수 等級制 실시에 따른 미생물학적 품질개선

姜國熙,朴信仁,鄭忠一 성균관대학교 생명과학자원연구소 1994 生命資源科學硏究 Vol.1 No.2

Raw milk grading system based on the bacterial count was started in Korea from June 1, 1993. The production ratio of first class which has 100,000/ml below in the bacterial counts of raw milk increased from 21% to 60% during 6 months. But, the ratio of the first class which has 250,000/ml below in the somatic cells did not change and became to be worse. In somatic cells the ratio of the first class milk was 42% in June 1993 and after 6 months it was decreased to 30%, Because current grade system based on the somatic cells give an penalty only to the off-grade milk which contains more of 750,000cell/ml. The system should be changed to pay different money according to the different classes of somatic cells in the raw milk.