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>

퇴행성 관절염에서 Interleukin-6와 Soluble Interleukin-6 Receptor

장재석 ( Jae Suk Chang ),정용갑 ( Yong Gab Jeong ),조우신 ( Woo Shin Cho ),빈성일 ( Seong Il Bin ),엄규황 ( Kyu Hwang Ym ),김정화 ( Jung Hwa Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.3

Objective: Unlike other soluble receptors, the soluble interleukin-6 receptor (sIL-6R) cooperates with IL-6 to activate gp130 of effector cell. As the IL-6 and sIL-6R are important in the rheumatoid disease, this study was designed to measure concentration of IL-6 and sIL-6R in synovium and synovial fluid of the degenerative arthritis. Methods: The synovium and synovial fluid were obtained during total knee replacement arthroplasty. The synovium was taken from eleven patients, and synovial fluid taken from sixteen patients. Same patients between two groups were seven. Tissue cultures of the synovial tissues were done with 10% FBS for 72 hours. After irrigation, thery were incubated for 48 hours without FBS, and the culture media and the synovial fluid were collected after centrifuged at 2500rpm for 10 minutes. The level of IL-6 and sIL-6R were measured by quantitative sandwich enzyme immunoassay technique. Results: In the synovium, the IL-6 level was 5.1±0.12ng/ml, and the sIL-6R level was 0.41±0.25ng/ml. In the synovial fluid, the IL-6 level was 0.09± 0.15ng/ml, and the sIL-6R level was 10.37±3.28ng/ml. These results show that IL-6 concentration was measured highly in two groups, especially in synovium (sixty times), and the sIL-6R concentration was measured significantly high in synovial fluid (twenty-five times). Conclusion: The IL-6 and sIL-6R were elevated in degenerative arthrits. We confirmed the source of IL-6 was synovium (very high in synovial tissue culture media), but we need further study for the source of sIL-6R as it was remarkably elevated as IL-6 and its level was lower than serum.

The Role of Cyclosporine and Mycophenolate in an Orthotopic Porcine-to-Rat Corneal Xenotransplantation

Hyeon Il Lee,김미금,오주연,Jung Hwa Ko,이현주,위원량,이진학 대한의학회 2008 Journal of Korean medical science Vol.23 No.3

We performed this study to investigate the feature of rejection in porcine-to-rat corneal orthotopic transplantation and to evaluate the effect of cyclosporine and mycophenolate on the xeno-rejection. Orthotopic corneal transplantation was done at 91 Sprague-Dawley rats, and they were divided into 10 groups based on the combination of immunosuppressants including dexamethasone, cyclosporine, and mycophenolate mofetil. Graft survival was analyzed and grafted eyes were examined with Hematoxylin & Eosin and CD4 or CD8 staining. Enzyme-linked immunosorbent assays were done for interleukin-2 (IL-2), IL-4, IL-5, IL-10, and interferon (IFN)-γin cornea, lacrimal gland, and cervical lymph nodes. The longest median survival of the immune suppressant group was 11.00±1.96 days, which showed no statistical differences compared with that of control (8.00±1.52 days). The neutrophils were prominent in the early phase but soon gave way to the monocytes. The number of CD8+ cells was higher than that of CD4+ cells. IL-2 and IFN-γmarkedly increased at 10 to13 days in cornea, lacrimal glands, and cervical lymph nodes, which showed a decrease with immunosuppressants except in the cornea. In conclusion, cyclosporine and mycophenolate could not prevent the rejection in porcine to rat orthotopic corneal xenograft associated with infiltraton of CD8+ and innate immune cells.

Interleukin-13 Increases Podocyte Apoptosis in Cultured Human Podocytes

Lee, Keum Hwa,Oh, Ji Young,Seong, Su-Bin,Ha, Tae-Sun,Shin, Jae Il Korean Society of Pediatric Nephrology 2018 Childhood kidney diseases Vol.22 No.1

Purpose: Podocytes are important architectures that maintain the crucial roles of glomerular filtration barrier functions. Despite this structural importance, however, the mechanisms of the changes in podocytes that can be an important pathogenesis of minimal change nephrotic syndrome (MCNS) are not clear yet. The aim of this study was to investigate whether apoptosis is induced by interleukin (IL)-13 in cultured human podocytes. Methods: Human podocytes were treated with different IL-13 doses and apoptotic cells were analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) and fluorescence-activated cell sorting (FACS). Results: The IL-13 increased the number of TUNEL-positive cells in a dose-dependent manner at 6 and 18 hours (P<0.05 and P<0.05, respectively). The apoptosis rate was appeared to be increased slightly in the IL-13-stimulated podocytes (8.63%, 13.02%, and 14.46%; 3, 10 and 30 ng/mL, respectively) than in the control cells (7.66%) at 12 hours by FACS assay. Conclusion: Our study revealed that IL-13 expression may increase podocyte apoptosis. Blocking the IL-13 signal pathway can potentially play an important role in regulating the apoptosis of podocytes.

The Role of Cyclosporine and Mycophenolate in an Orthotopic Porcine-to-Rat Corneal Xenotransplantation

Lee, Hyeon Il,Kim, Mee Kum,Oh, Joo Youn,Ko, Jung Hwa,Lee, Hyun Ju,Wee, Won Ryang,Lee, Jin Hak The Korean Academy of Medical Sciences 2008 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.23 No.3

<P>We performed this study to investigate the feature of rejection in porcine-to-rat corneal orthotopic transplantation and to evaluate the effect of cyclosporine and mycophenolate on the xeno-rejection. Orthotopic corneal transplantation was done at 91 Sprague-Dawley rats, and they were divided into 10 groups based on the combination of immunosuppressants including dexamethasone, cyclosporine, and mycophenolate mofetil. Graft survival was analyzed and grafted eyes were examined with Hematoxylin & Eosin and CD4 or CD8 staining. Enzyme-linked immunosorbent assays were done for interleukin-2 (IL-2), IL-4, IL-5, IL-10, and interferon (IFN)-γ in cornea, lacrimal gland, and cervical lymph nodes. The longest median survival of the immune suppressant group was 11.00±1.96 days, which showed no statistical differences compared with that of control (8.00±1.52 days). The neutrophils were prominent in the early phase but soon gave way to the monocytes. The number of CD8+ cells was higher than that of CD4+ cells. IL-2 and IFN-γ markedly increased at 10 to13 days in cornea, lacrimal glands, and cervical lymph nodes, which showed a decrease with immunosuppressants except in the cornea. In conclusion, cyclosporine and mycophenolate could not prevent the rejection in porcine to rat orthotopic corneal xenograft associated with infiltraton of CD8+ and innate immune cells.</P>

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.

제대혈 유래 인간 비만세포에서의 세포증식 및 히스타민 분비에 대한 Interleukin 9의 영향

안강모 ( Kang Mo Ahn ),이광신 ( Kwang Shin Lee ),신미용 ( Mi Yong Shin ),박화영 ( Hwa Young Park ),안연화 ( Yeon Hwa Ahn ),손대열 ( Dae Yeul Son ),이상일 ( Sang Il Lee ) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2002 소아알레르기 및 호흡기학회지 Vol.12 No.4

목적: Interleukin 9(IL-9)는 Th2 싸이토카인의 일종으로서 알레르기 염증반응의 병태생리에 관여하는 것으로 알려져 있다. 본 연구에서는 IL-9이 주요 알레르기 염증세포의 하나인 인간 비만세포에 어떠한 영향을 주는지를 알아보기 위하여 시행되었다. 방법:본 연구에서는 인간 제대혈에서 CD34 (+) 세포를 분리한 후 stem cell factor(SCF), IL-3, IL-6를 투여함으로써 비만세포를 선택적으로 배양하였다. 8주간 배양이 끝 Purpose:Interleukin-9(IL-9), one of Th2-type cytokines, might be important in the pathophysiology of allergic diseases. We investigated the effect of IL-9 on human mast cells by assessing cell proliferation and histamine release. Methods: Human umbilical

Studies of cocktail therapy with multiple cytokines for neoplasia or infections disease of the dog I. cDNA cloning of canine IL-3 and IL-6

Il Seob Shin,Hye Ryon Kim,Myung Jin Nam,Hwa Young Youn 대한수의학회 2001 Journal of Veterinary Science Vol.2 No.2

유가증권시장 상장기업의 선택적 회계처리에 관한 실태 분석

이병화 ( Lee Byung-hwa ),윤우영 ( Yun Woo-young ),정원일 ( Jung Won-il ) 한국세무회계학회 2017 세무회계연구 Vol.0 No.52

본 연구는 한국거래소 유가증권시장에 상장된 기업의 유형자산과 재고자산의 선택적 회계처리에 관한 실태 분석이다. 유형자산의 평가모형 및 감가상각방법 분석결과 유형자산의 평가모형 중 원가모형을 적용하고 있는 회사는 전체 728개 중 659개(90.5%), 64개(8.8%)가 원가모형과 재평가모형을 함께 적용하고 있다. 재평가모형을 적용하는 유형자산은 대부분 토지로 나타나고 있으며, 재평가모형만을 적용하는 회사는 없는 것으로 나타났다. 유형자산의 감가상각방법 중 정액법을 적용하고 있는 회사는 전체 728개 중 709개(97%), 정액법과 정률법을 함께 적용하는 회사는 11개(1.5%), 정액법과 생산량비례법을 함께 적용하는 회사는 2개, 정률법만 적용하는 회사는 1개 회사로 나타났다. 그리고 3개 회사는 유형자산 계정과목이 없으며, 2개 회사는 감가상각방법에 대한 내용이 주석에 공시되지 않고 있다. 재고자산의 수량결정방법과 가격결정방법을 분석한 결과 재고자산의 수량결정방법으로 계속 기록법과 실지재고조사법을 함께 적용하고 있는 회사는 728개 중 68개(9.3%), 실지재고조사법만 적용하는 회사는 3개, 계속기록법만 적용하는 회사는 1개 회사이다. 나머지 548개(75.3%) 회사는 주석에 수량결정방법을 공시하지 않고 있다. 재고자산의 가격결정방법은 회사들이 기업의 환경에 맞게 재고자산의 유형에 따라 다양하게 적용하고 있으며, 업종의 특성에 따라 금융업과 서비스업 중 지주회사에 해당하는 기업에서는 재고자산 계정과목이 재무상태표에 나타나지 않고 있으며, 유통업에서는 소매재고법(매출가격환원법)을 적용하는 회사가 9개 회사로 나타났다. 유형자산의 경우는 업종 특성에 관계없이 대부분의 회사가 평가모형으로 원가모형, 감가상각방법으로 정액법을 사용하고 있으며, 이와 달리 재고자산의 경우는 기업의 상황과 업종 특성을 반영하여 다양한 가격결정방법을 사용하고 있는 것으로 판단된다. This study is an analysis on the realities on the selective accounting of property, plant and equipment and inventories of listed firms in KOSPI. As a result of analyzing the evaluation model and depreciation method of property, plant and equipment, 659 firms(90.5%) out of the total 728 firms that applied cost model. and 64 firms(8.8%) applied cost model and revaluation model. Most of the property, plant and equipment applying the revaluation model are shown as land, and no firm applies the revaluation model. Among depreciation methods of property, plant and equipment, 706 firms(97%) of the total 728 firms that apply the straight-line method, 11 firms(1.5%) to apply the straight-line method and the fixed percentage method. There are two firms that apply the straight-line method and activity method, one firm that applies only the fixed percentage method. The three firms do not have a property, plant and equipment account and the two firms do not disclose depreciation methods in the footnotes. As a result of analyzing the method of determining the quantity of inventories and the method of determining the price, 68 firms(9.3%) of the 728 firms that applied perpetual inventory system and periodic inventory system. There are three firms that applies only periodic inventory system, and one firm that applies only perpetual inventory system. The remaining 548 firms(75.3%) do not disclose how to determine the amount in the financial statements footnotes. The method of determining the price of inventories varies according to the types of inventories according to the firm`s environment. According to the characteristics of the industry, firms in the financial and service industries that are holding companies do not show inventory account in their financial statements. In the retail industry, six firms apply the retail inventory method.

Scoparone from Artemisia capillaris Inhibits the Release of Inflammatory Mediators in RAW 264.7 Cells upon Stimulation Cells by Interferon-γ Plus LPS

Seon Il Jang,Young-Jun Kim,Woo-Yiel Lee,Kyung Chell Kwak,Seung Hwa Baek,Gyu Beum Kwak,Young-Gab Yun,Tae-Oh Kwon,Hun Taeg Chung,Kyu-Yun Chai 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.2

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) upon stimulation by IFN-γ/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-γ/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and PGE2 in macrophages by inhibiting iNOS and COX-2 expression.