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>

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>

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.

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.

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.

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.

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.

Monosodium Iodoacetate로 유발한 골관절염 흰쥐에 대한 여지초(荔枝草)의 효능 평가

이수화 ( Lee Soo Hwa ),서부일 ( Seo Bu-il ) 한약응용학회 2021 한약응용학회지 Vol.21 No.1

Salviae Plebeiae Herba (SP) contains a numberous chemical components and reported to exert various pharmacological activities such as antioxidant, anti-inflammatory, antimicrobial, analgesic, hypoglycemic, antiviral, anti-tumour, and hepatoprotective effects. Even though it has these various effects, its scientific proof remains uncertain the effect and underlying mechanism about joint damage. Accordingly, the present study was designed to evaluate the therapeutic effects and possible underlying mechanism of SP on osteoarthritis. OA models were induced via intra-joint injection of monosodium iodoacetate (MIA) 50 ㎕ with 80 ㎎/㎖ in rats. Excluding the normal group, OA-induced mice were divided into 4 groups (control, INDO, SPL, SPH). The drug concentrations were indomethacin 5 ㎎/㎏, SP 500 ㎎/㎏, and SP 1000 ㎎/㎏, and were administered orally once a day for 2 weeks. After drug supplementation, the effects of SP were measured with serum analysis, western blotting, and histopathological staining. SP administration improved hind limb overload and it led to relieve pain. Moreover, it suppressed oxidative related factors. The NF-κB inactivation though the inhibition of IκBα phosphorlyation significantly decreased both inflammatory mediators such as COX-2 and iNOS and cytokines such as TNF-α, IL-1β, and IL-6. Whereas, anti-inflammatory cytokines like IL-4 and IL-10 were shown to increase. In addition, SP administration exerted a protective effect on ECM by reducing the expression of collagen degradation factors including MMP-1, -3, -13 and by increasing TIMP-1. Taken together, SP may possess the effect of delaying the progression of osteoarthritis and protecting cartilage. Accordingly, the present study may provide a scientific basis the chondroprotective effect of SP on MIA induced osteoarthritis.

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.

고종시 감나무 부위별 수용성 추출물의 항산화 및 항염 활성

전인화(In Hwa Jeon),강현주(Hyun Ju Kang),이현서(Hyun-Seo Lee),신준호(Jun Ho Shin),박용균(Yong Gyoun Park),정승일(Seung-Il Jeong),장선일(Seon Il Jang) 한국식품과학회 2014 한국식품과학회지 Vol.46 No.4

본 연구는 고종시 감나무 부위별 수용성 추출물의 항산화 및 항염증에 대한 효과를 조사하였다. 감꼭지와 감잎은 DPPH, ABTS 및 NO 등 라디칼을 효과적으로 제거하는 활성뿐만 아니라 환원력도 우수한 항산화 활성을 보였다. 또한 LPS에 의해 활성화된 설치류 유래 대식세포주인 RAW 264.7 세포에서 NO 생성억제는 감꼭지 추출물이 가장 우수하였지만, PGE₂ 생성의 경우 모든 부위의 추출물에서 탁월한 억제 효과가 있었다. 더욱이 활성화된 RAW 264.7 세포에서 감꼭지, 감잎 및 감껍질 추출물은 농도에 의존적으로 TNF-α와 IL-1β를 효과적으로 억제하였다. 이러한 결과는 고종시 감나무 부위별 추출물 중 감꼭지와 감잎은 항산화제뿐만 아니라 항염증에 효과적인 물질이라는 것을 제시해주었고, 감껍질의 경우 비록 항산화 효과는 낮았지만, 우수한 항염효과를 나타내는 물질임을 제시해주었다. 그러므로 고종시 감나무수용성 추출물은 항산화와 항염 기능을 발휘할 수 있는 식품으로 활용될 수 있을 것이라 사료된다. Kojongsi persimmon (Diospyros kaki L.) is the major cultivar of dried persimmon in Korea. The purpose of this study was to investigate the antioxidant and anti-inflammatory activities of water-soluble extracts from the calyx (PCE), peel (PPE) and leaf (PLE) of Kojongsi persimmon. PCE showed the highest total phenolic and flavonoid contents. In addition, the antioxidant activities (diphenylpicrylhydrazyl, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), nitric oxide and reducing power) of PCE were higher than those of PPE and PLE. Moreover, PCE, PPE and PLE significantly suppressed the production of inflammatory mediators (nitric oxide and prostaglandinE₂) and pro-inflammatory cytokines (tumor necrosis factor-α and interluekin-1β) by lipopolysaccharide-stimulated RAW 264.7 cells in a dose-dependent manner. PCE showed the highest anti-inflammatory activity. Thus, these results suggest that the calyx of Kojongsi persimmon may be highly valuable as a natural product owing to its high-quality functional components as well as its-antioxidant, antiinflammatory activities.