IL-15에 의한 류마티스관절염 환자 활막 섬유모세포에서의 SDF-1 유도

박영은 ( Young Eun Park ),김성일 ( Sung Il Kim ),박성후 ( Seong Hu Park ),백승훈 ( Seung Hoon Baek ),오혜좌 ( Hye Jwa Oh ),허양미 ( Yang Mi Heo ),조미라 ( Mi La Cho ) 대한류마티스학회 2010 대한류마티스학회지 Vol.17 No.3

Objective: Interleukin-15 (IL-15) recruits and activates synovial T cells, and IL-15 plays an important role in amplifying and perpetuating inflammation in the pathogenesis of rheumatoid arthritis (RA). Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for memory T cells in the inflamed RA synovium. This study investigated the effect of IL-15 on SDF-1 production in RA fibroblast-like synoviocytes (FLS). Methods: The expressions of IL-15 and SDF-1 were determined from the synovium of patients with RA and osteoarthritis (OA) by performing immunohistochemistry. The expressions of SDF-1 was measured from the RA FLS that were cultured with IL-15 and IL-17 by real-time RT-PCR and ELISA. The SDF-1 expression was also measured, via ELISA, from the RA FLS stimulated by IL-15 together with the inhibitors of such intracellular signal molecules as phosphatidylinositol 3-kinase (PI 3-kinase, LY294002), STAT3 (AG490), MAP Kinase (PD98059), NF-κB (parthenolide) and activator protein 1 (AP-1, curcumin). Results: IL-15 and SDF-1 were mainly expressed in the RA synovium compared to that of the OA synovium. IL-15 increased the SDF-1 expressions and it, and had an additive effect with IL-17 on the SDF-1 expressions in the cultured RA FLS. The IL-15 induced increase of the SDF-1 expression in the cultured RA FLS was blocked by the inhibitors of PI 3-kinase, NF-κB and AP-1. Conclusion: The SDF-1 expression was increased in the RA synovium and it was up-regulated by IL-15 in the RA FLS through the PI 3-kinase, NF-κB, and AP-1 pathways. These results imply that the IL-15 induced increase of the SDF-1 expressions may be involved in the immunopathogenesis of RA.

류마티스 관절염 동물 모델에서 활막의 RANKL/OPG mRNA 발현 비율 및 IL-17의 효과

이준희 ( Jun Hee Lee ),김근태 ( Geun Tae Kim ),류선 ( Sun Ryu ),김주인 ( Ju In Kim ),백승훈 ( Seung Hoon Baek ),김성일 ( Sung Il Kim ) 대한류마티스학회 2006 대한류마티스학회지 Vol.13 No.2

Objective: To investigate the synovial mRNA expression of receptor activator of NFκB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG) and RANKL/OPG mRNA expression ratio, and to evaluate the effects of IL-17 in experimental rheumatoid arthritis (RA) model. Methods: After induction of collagen-induced arthritis (CIA) by type II collagen in DBA1 mice, mice were anesthetized at day 28 and a small aperture in the skin of the knee was performed. Mice, in which arthritis of knee was present, were selected and divided into 3 groups, and phosphate-buffered saline (PBS group), IL-17 (IL-17 group) or anti-IL-17 monoclonal antibody (anti-IL-17 group) was injected to both knee joint at day 28 and 32. At day 35, mice were sacrificed and synovium of knee joints were isolated. Synovial mRNA expression of RANKL, RANK and OPG was assessed by real-time RT-PCR and immunohistochemical stain. Results: Synovial RANKL and RANK mRNA expressions were significantly different among IL-17, PBS, anti-IL-17 and normal group (IL-17>PBS>anti-IL-17>normal group), and synovial OPG mRNA expressions in PBS, IL-17 and anti-IL-17 group were significantly high than those in normal group, however, there was no significant difference among IL-17, PBS and anti-IL-17 group. RANKL/OPG mRNA ratio was significantly different among these groups (IL-17>PBS>anti-IL-17>normal group). In immunohistochemical stain, RANKL, RANK and OPG-positive cells were expressed at synovium. Conclusion: Synovial RANKL/OPG mRNA ratio was enhanced in CIA, and IL-17 induced higher RANKL/OPG ratio in the synovium of CIA, which was blocked by anti-IL-17 antibody. These results suggest that RANKL/OPG mRNA ratio play an important roles on bone destruction, and IL-17 may be actively involved in bone destruction by enhancing RANKL/OPG ratio in CIA model.

Interleukin-17이 배양된 류마티스관절염 활막세포에서 vascular endothelial growth factor 생성에 미치는 영향

곽임수 ( Ihm Soo Kwak ),남태수 ( Tae Soo Nam ),나하연 ( Ha Yeon Rha ),서정탁 ( Jeung Tak Suh ),김유선 ( Yoo Sun Kim ),김성일 ( Sung Il Kim ) 대한류마티스학회 2001 대한류마티스학회지 Vol.8 No.3

Objective: To investigate the the effects of interleukin-17 (IL-17) on the production of vascular endothelial growth factor (VEGF) from cultured rheumatoid arthritis synoviocytes. Methods: Fibroblast-like synovial cells(FLS) were prepared from the synovial tissues of rheumatoid arthritis patients and cultured in the presence of IL-17, IL-17 with or without transforming growth factor-β(TGF-β), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β). VEGF levels were determined in the culture supernatants by sandwitch ELISA. Results: Stimulation of FLS by serial concentration of IL-17, TGF-β, TNF-α, IL-1β increased the production of VEGF by 2.1-2.7, 2.2-3.0, 2.0-2.9, 2.3-3.1 fold over the constitutive levels of unstimulated FLS. Stimulation of FLS by IL-17 with TGF-β or TNF-α or IL-1β also increased the production of VEGF according to culture periods by 1.6-1.8, 1.1-1.9, 1.5-1.7 fold over the levels stimulated with TGF-β or TNF-α or IL-1β, respectively. This results indicated that IL-17 increased the effect of TGF-β, TNF-α, IL-1β on FLS, leading synergistic enhancement of VEGF production. Conclusion: IL-17 may be involved in the neovascularization in rheumatoid synovitis by enhancing the production of VEGF.

자유기에 의한 지질과산화 반응에 대한 황금 약침액의 항산화 효능

김성일,문진영,김갑성,김두희,남경수,임종국,Kim Sung-Il,Moon Jin-Young,Kim Kap-Sung,Kim Doo-Hie,Nam Kyung-Soo,Lim Jong-Kook 대한예방한의학회 1997 대한예방한의학회지 Vol.1 No.1

Scutellariae radix, has been used as a natural drug for fever, inflammation, cataract, and liver disease in traditional medicine. This study was performed in order to investigate the antioxidative effects of Scutellariae radix aqua-acupuncture solution (SRAS) on lipid peroxidation by free radicals. Lipid peroxidation levels were determined by TBA method during the autoxidation of linoleic acid. In this linoleic acid autoxidation system, SRAS markedly exhibited antioxidant activity, which inhibited 89% of linoleic acid peroxidation. SRAS showed scavenging effects on ${\alpha},{\alpha}-diphenyl-{\beta}-picrylhydrazyl$(DPPH) radical, inhibited superoxide generation in xanthine-xathine oxidase system, and also inhibited lipid peroxidation of rat liver tissue by hydroxyl radical derived from $H_2O_2-FE^{+2}$ system. These effects were similar to those of $dl-{\alpha}-tocopherol$, BHA and BHT. In addition, SRAS protected the cell death induced by ter-butyl hydroperoxide (t-BHP) and significantly increased cell viability in the normal rat liver cell (Ac2F). On the basis of these results, it is suggested that SRAS might play a protective role in lipid peroxidation by free radicals.

사료 내 생 미강과 볶은 대두의 첨가가 거세한우 등심의 이화학적 특성과 관능적 특성에 미치는 영향

김성일,정근기,김덕영,김진열,최창본,Kim, Sung-Il,Jung, Keun-Ki,Kim, Duck-Young,Kim, Jin-Yeoul,Choi, Chang-Bon 한국축산식품학회 2011 한국축산식품학회지 Vol.31 No.3

본 연구는 거세한우 사료 내 미강과 볶은 대두를 첨가 함으로써 거세한우 도체등심의 이화학적 특성과 관능적 특성에 미치는 영향을 조사하고자 실시되었다. 평균 20.92개월령(평균체중 599.89 kg)의 거세한우 36두를 대조구, 시험 1구(미강 첨가구) 및 시험 2구(볶은 대두 첨가구)로 나누고 각각의 처리구는 체중 및 월령을 고려하여 배치하였다(12두/처리구). 미강과 볶은 대두의 첨가 수준은 시험 사료 내 조지방 함량을 5%로 설정하고, 조지방 부족분을 각각의 첨가원료(미강과 볶은 대두)로부터 보충 되도록 설계하였으며, 시험동물이 평균 31.2개월령에 도달할 때까지 314일간 사양시험을 실시하였다. 도체등심의 일반 조성분은 처리구별 뚜렷한 차이는 없었고 가열 감량과 드립 감량도 처리구별 유의적인 차이는 없었다. 체지방 부위에 따른 처리구별 융점은 뚜렷한 차이가 없었으나, 체지방 부위별 융점은 등심지방($25.83-26.17^{\circ}C$), 피하지방($17.26-18.53^{\circ}C$) 및 신장지방($32.40-33.15^{\circ}C$)이 서로 다른 범위를 나타내었다. 도체등심의 단맛과 관련이 있는 유리 아미노산은 시험 1구가 39.48 mg/100 g으로서 대조구의 32.24mg/100 g에 비하여 유의적(p<0.05)으로 높게 나타났으며, 쓴맛과 관련이 있는 유리 아미노산은 시험 2구가 25.93mg/100 g으로서 다른 처리구에 비하여 유의하게(p<0.05) 낮게 나타났다. 도체등심의 지방산 조성 중 $C_{14:0}$, $C_{16:0}$, $C_{16:1}$, $C_{18:0}$ 및 $C_{18:1}$의 함량은 처리구별 유의적인 차이가 없었으며, 다가불포화지방산인 $C_{20:3}$은 시험 2구가 다른 처리구에 비하여 유의적(p<0.05)으로 높게 나타났다. 도체등심의 관능평가 결과는 다즙성의 경우 시험 1구가 가장 높게 나타났으며(p<0.05), 종합기호 도의 경우는 시험 1구와 시험 2구가 대조구에 비하여 유의적으로(p<0.05) 높게 나타났다. 도체등심의 관능 평가 항목들과 주요지방산 조성간의 상관관계는 $C_{18:1}$은 연도와, $C_{18:0}$은 풍미와 정(+)의 상관관계(각각 r=0.650 및 0.698; p<0.05)를 나타내었다. 이상의 연구 결과를 종합해 보면 사료 내 미강과 볶은 대두의 첨가가 거세한우 등심의 이화학적 특성에는 처리구별 뚜렷한 차이를 보이지 않았지만 관능적 특성을 개선시키는 데에는 효과적이었던 것으로 나타났다. We investigated melting points and sensory characteristics by adding rice bran and roasted soybean to the finishing diet of Hanwoo steers. Thirty-six Hanwoo steers (average age, 20.92 mon-old; average weight, 599.89 kg) were assigned to either Control, Treatment 1 (rice bran) or Treatment 2 (roasted soybean) groups (12 steers/group), considering body weight and age. Supplementation levels of rice bran and roasted soybean were determined to meet total 5% crude fat in the concentrates, and the experimental animals were fed for 314 d until they reached 31.2 mon old. No significant differences were found in the moisture and crude fat content among groups. Melting points of lipid extracted from M. longissimus dorsi, subcutaneous fat, and perirenal fats were 25.83-26.17, 17.26-18.53 and $32.40-33.15^{\circ}C$, respectively, resulting in remarkable differences depending on fat depots. Contents of free amino acids in M. longissimus dorsi related to sweet taste were 39.48 mg/100 g for Treatment 1, which was significantly (p<0.05) higher than those for Control (32.24 mg/100 g), whereas those related to bitter taste were 25.93 mg/100 g for Treatment 2, which was the lowest (p<0.05) among the groups. Fatty acid composition, such as $C_{14:0}$, $C_{16:0}$, $C_{16:1}$, $C_{18:0}$, and $C_{18:1}$, in M. longissimus dorsi was not different among the groups. Results of a panel test on M. longissimus dorsi showed that Treatment 1 scored the highest (p<0.05) in juiciness, and both Treatments 1 and 2 scored higher (p< 0.05) in overall palatability than the Control group. $C_{18:1}$ showed a positive (+) relationship with tenderness (r = 0.650; p<0.05), and $C_{18:0}$ with flavor (0.698; p<0.05). The results suggest that rice bran and roasted soybean are beneficial for improving M. longissimus dorsi sensory characteristics, whereas no significant differences were found in the physico-chemical characteristics among the groups.

류마티스 활막염에 있어 염증매개물질에 의한 Transforming Growth Factor-β-inducible Gene-h3 (βig-h3) 생산 조절 기전

강영모 ( Young Mo Kang ),김성일 ( Sung Il Kim ),김정섭 ( Jeong Seup Kim ),유동완 ( Dong Wan You ),사금희 ( Kheum Hee Sa ),박은주 ( Eun Ju Park ),김성욱 ( Sung Uk Kim ),서재석 ( Jae Seok Seo ),한승우 ( Seung Woo Han ),남언정 ( Eon 대한류마티스학회 2005 대한류마티스학회지 Vol.12 No.2

Objective: To investigate the expression pattern of transforming growth factor-β-inducible gene-h3 (βig-h3) within rheumatoid synovial tissue and the regulation of βig-h3 synthesis in fibroblast-like synoviocyte (FLS). Methods: Synovial tissues obtained from patients with rheumatoid arthritis and osteoarthritis were obtained during joint replacement surgery. βig-h3 expression was evaluated with immunohistochemical stain. FLS was isolated from synovial tissues and stimulated with cytokines including TGF-β, TNF-α, IL-1β, IFN-γ, IL-6, IL-4, and IL-10. βig-h3 synthesis was measured using semiquantitative RT-PCR, ELISA, immunofluorescence stain, and flow cytometry. Results: Expression of βig-h3 was diffuse and abundant in both lining and sublining layers of rheumatoid synovium, which was more prominent than those of osteoarthritis. Production of βig-h3 in FLS was regulated by TGF-β1 in a dose-dependent manner and was highest at 5 ng/mL of TGF-β1. TNF-α and IL-1β upregulated the production of βig-h3 from FLS synergistically with TGF-β1 but other cytokines such as IL-4, IL-6, IL-10 did not affect. βig-h3 synthesis was efficiently inhibited by dexamethasone at higher dose (100 nM) but not by cyclosporine-A. Conclusion: Production of βig-h3, which is highly upregulated in rheumatoid synovitis, is differentially regulated by inflammatory cytokines.

특발성 염증성 근육병증 환자에서 IL-17 발현의 증가

백승훈 ( Seung Hoon Baek ),이준희 ( Jun Hee Lee ),김근태 ( Geun Tae Kim ),이정욱 ( Joung Wook Lee ),조미라 ( Mi Ra Cho ),김주인 ( Ju In Kim ),이선희 ( Sun Hee Lee ),김대성 ( Dae Seong Kim ),김성일 ( Sung Il Kim ) 대한류마티스학회 2008 대한류마티스학회지 Vol.15 No.2

Objective: Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterized by infiltration of T lymphocytes, monocytes, and macrophages in muscle tissues. Interleukin-17 (IL-17), a Th17 cytokine, has potent pro-inflammatory actions and plays a role in autoimmune diseases. We investigated the expression of IL-17 in muscle tissues of patients with IIMs. Methods: We measured the IL-17 mRNA level of muscle tissues from 14 patients with IIMs (9 patients with dermatomyositis and 5 patients with polymyositis) by real-time RT-PCR and compared with controls. We also performed an immunohistochemical stain to detect IL-17 expression. Results: The expressions of IL-17 were significantly enhanced in IIMs than controls. In immunohistochemistry, IL-17 was expressed in perimysial, endomysial and perivascular infiltrating inflammatory cells. Conclusion: These results suggest that IL-17 plays a role in the immunopathogenesis of IIMs.

Interleukin-17이 배양된 류마티스 관절염 활막세포에서 Matrix Metalloproteinase-3의 생성에 미치는 영향

류선 ( Sun Ryu ),김성일 ( Sung Il Kim ) 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.1

Objective: To investigate the effect of interleukin-17 (IL-17) on the production of matrix metalloproteinase-3 (MMP-3) and the expression of MMP-3 mRNA in rheumatoid arthritis synoviocytes. Methods: Fibroblast-like synovial cells (FLS) were prepared from the synovial tissues of rheumatoid arthritis patients and cultured in the presence of various concentration of IL-17. The production of MMP-3 and expression of MMP-3 mRNA were determined by sandwitch ELISA and real-time quantitative RT-PCR. Results: In ELISA, stimulation of FLS by IL-17 with 5, 10, 20, 40 ng/mL concentrations increased the production of MMP-3 by 2.7, 2.9, 3.1, 3.6 fold after 24 hours and 9.9, 10, 11, 12 fold after 48 hours over the constitutive levels of unstimulated FLS. In real-time quantitative RT-PCR, stimulation of FLS by IL-17 with 5, 10, 20, 40 ng/mL concentrations increased the MMP-3/β-actin mRNA ratio by 3.2, 5.7, 9.9, 30.5 fold after 24 hours over the constitutive levels of unstimulated FLS.

류마티스 관절염 동물 모델에서 Toll-Like Receptors의 발현

이준희 ( Jun Hee Lee ),이수봉 ( Soo Bong Lee ),김근태 ( Geun Tae Kim ),류선 ( Sun Ryu ),김주인 ( Ju In Kim ),이선희 ( Sun Hee Lee ),김성일 ( Sung Il Kim ) 대한류마티스학회 2006 대한류마티스학회지 Vol.13 No.2

Objective: To evaluate the expression of Toll-like receptor (TLR) 2, 4 and 9 and investigate the effects of IL-17 on the expression of TLRs in experimental rheumatoid arthritis (RA) model. Methods: After induction of collagen-induced arthritis (CIA) by type II collagen in DBA1 mice, phosphate-buffered saline (PBS, PBS group) or IL-17 (IL-17 group) was injected to both knee joint at day 28 and 32. At day 35, mice were sacrificed and knee joints were isolated. Synovial mRNA expressions of TLR-2, 4 and 9 determined by real-time RT-PCR were compared among normal DBA1 mice (normal group), PBS and IL-17 group. Results: Synovial TLR-2, 4, and 9 mRNA expressions of IL-17 and PBS group were significantly higher than normal group, and those of IL-17 group were higher than PBS group. Conclusion: Synovial TLR-2, 4 and 9 expression was enhanced in CIA and up-regulated by local overexpression of IL-17. These results suggest that TLRs play a roles on CIA and IL-17 induced aggravation of arthritis in CIA.

라미네이트 도재와 복합레진 시멘트의 결합강도에 관한 연구

김성일,임호남,박남수,Kim, Sung-Il,Lim, Ho-Nam,Park, Nam-Soo 대한치과보철학회 1991 대한치과보철학회지 Vol.29 No.1

The purpose of this study were to comfirm the effects of the thickness and kinds of porcelain, etchants, illumination time, elapsed time for the measurement, and chemical cure component to the bond strength of porcelain laminate and composite resin cement, and to compare the effects between the light cured resin and the dual cured resins. The etched porcelain surface, the sectioned surface crossing porcelain and resin after bonding, and the debonded surfaces were observed by the SEM. One product of laminate porcelain powder, one light cured resin and two dual cured resins were selected. Each resin cements are lightened through the thin porcelain disc which was cut from cylindrical porcelain specimen by the diamond saw, and by the light through the porcelain disc they were bonded. Changes of thickness and kinds of porcelain, etchants, illumination time, and the elapsed time for the measurement were considered as variables for the bond strength. And the bond strength of porcelain and dual cured resins under the conditions of autopolymerization or the removal of chemical cure component were measured and compared. Bond strength were measured by shear stress. The etched surface, the cross-sectioned surface, and the debonded surface of porcelain or resin were observed by SEM. On the summary of this study, the following conclusions can be stated; 1. Bond strength of light cured resin was decreased inversely by the thickened porcelain laminate and showed the lowest value to the masking dentin porcelain among 4 kinds of porcelain powder. 2. Bond strength of autopolymerization of dual cured resin without illumination in dark chamber were from 75% to 98% to the data of dual cured resin with illumination. 3. Bond strength of dual cured resin used without chemical cured components were same to them of light cured resin. 4. Cross-sectioned surface treated by silane did not show the gap between the porcelain and resin. 5. Illumination over 80 seconds did not make the significant increase of bond strength on all kinds of resin.