Interleukin 17 (IL-17) Increases the Expression of Toll-like Receptor-2, 4, and 9 by Increasing IL-1β and IL-6 Production in Autoimmune Arthritis

LEE, JUN-HEE,CHO, MI-LA,KIM, JU-IN,MOON, YOUNG-MEE,OH, HYE-JWA,KIM, GEUN-TAE,RYU, SUN,BAEK, SEUNG-HOON,LEE, SUN-HEE,KIM, HO-YOUN,KIM, SUNG-IL The Journal of Rheumatology 2009 The Journal of rheumatology Vol.36 No.4

<B>Objective.</B><P>To examine the effect of interleukin 17 (IL-17) on the expression of Toll-like receptor (TLR)-2, 4, and 9 in collagen-induced arthritis (CIA) in mice.</P><B>Methods.</B><P>On Days 28 and 32 after induction of CIA in mice, phosphate-buffered saline (PBS group) or IL-17 (IL-17 group) was injected into both knee joints. On Day 35, mice were sacrificed. The severity of knee joint arthritis, synovial inflammation, and bone destruction was measured by a scoring system using macrography and histological analysis. Synovial expression of TLR-2, 4, 9, IL-17, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-6 was determined by real-time PCR and immunohistochemistry. Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing antibodies to cytokine, and the expression of TLR-2, 4, 9, IL-1ß, TNF-α, and IL-6 was determined by real-time RT-PCR.</P><B>Results.</B><P>In CIA mice, knee arthritis scores, synovial inflammation, bone destruction scores, and expression of synovial TLR-2, 4, and 9, IL-17, IL-1ß, TNF-α and IL-6 were higher in the IL-17 and PBS groups than in normal DBA1 mice. These variables were also significantly higher in the IL-17 group than in the PBS group. In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9, and this effect was significantly alleviated by neutralizing antibodies to IL-17, IL-1ß, and IL-6.</P><B>Conclusion.</B><P>IL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1ß and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1ß and IL-6 production are involved in the IL-17-induced aggravation of arthritis.</P>

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.

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.

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.

Expression of TLR2, TLR4, and TLR9 in dermatomyositis and polymyositis

Kim, Geun-Tae,Cho, Mi-La,Park, Young-Eun,Yoo, Wan Hee,Kim, Jung-Hee,Oh, Hye-Jwa,Kim, Dae-Sung,Baek, Seung-Hoon,Lee, Sun-Hee,Lee, Jun-Hee,Kim, Ho-Youn,Kim, Sung-Il Springer-Verlag 2010 CLINICAL RHEUMATOLOGY Vol.29 No.3

<P>The aim of this study was to investigate the expressions of Toll-like receptor (TLR) 2, TLR4, TLR9, and their correlations with the expression of cytokines that are associated with activation of CD4<SUP>+</SUP> T cells and inflammation including interferon γ (IFNγ), interleukin 4 (IL4), interleukin 17 (IL17), and tumor necrosis factor α (TNFα) in muscle tissues of patients with dermatomyositis (DM) and polymyositis (PM). The expressions of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were measured by real-time reverse transcription–polymerase chain reaction in muscle tissues from 14 patients with DM and PM (nine patients with DM, five patients with PM) and three controls. The expressions of TLR2, TLR4, and TLR9 were also localized with immunohistochemistry. The expression levels of TLR2, TLR4, TLR9, IFNγ, IL4, IL17, and TNFα were significantly high in patients with DM and PM compared with those in the controls, and the expression levels of TLR4 and TLR9 had significant positive correlations with the expressions of IFNγ, IL4, IL17, and TNFα. Immunohistochemistry showed that TLR2, TLR4, and TLR9 were expressed by infiltrating cells of perimysium in DM, whereas they were expressed by infiltrating cells of endomysium in PM. These results suggest that the involvement of TLR4 and TLR9 in immunopathogenesis of DM and PM might be connected with activation of CD4<SUP>+</SUP> T cells.</P>

IRAK4 as a Molecular Target in the Amelioration of Innate Immunity–Related Endotoxic Shock and Acute Liver Injury by Chlorogenic Acid

Park, Sun Hong,Baek, Seung-Il,Yun, Jieun,Lee, Seungmin,Yoon, Da Young,Jung, Jae-Kyung,Jung, Sang-Hun,Hwang, Bang Yeon,Hong, Jin Tae,Han, Sang-Bae,Kim, Youngsoo American Association of Immunologists 2015 Journal of Immunology Vol. No.

<P>Mice lacking the IL-1R-associated kinase 4 (IRAK4) are completely resistant to LPS-induced endotoxic disorder or the TLR9 agonist CpG DNA plus D-galactosamine-induced acute liver injury (ALI), whereas wild-type strains succumb. However, translational drugs against sepsis or ALI remain elusive. Lonicerae flos extract is undergoing the clinical trial phase I in LPS-injected healthy human volunteers for sepsis treatment. In the current study, chlorogenic acid (CGA), a major anti-inflammatory constituent of lonicerae flos extract, rescued endotoxic mortality of LPS-intoxicated C57BL/6 mice, as well as ameliorated ALI of LPS/D-galactosamine-challenged C57BL/6 mice. As a mechanism, CGA inhibited various TLR agonist-, IL-1 alpha-, or high-mobility group box-1-stimulated autophosphorylation (activation) of IRAK4 in peritoneal macrophages from C57BL/6 or C3H/HeJ mice via directly affecting the kinase activity of IRAK4, a proximal signal transducer in the MyD88-mediated innate immunity that enhances transcriptional activity of NF-kappa B or AP-1. CGA consequently attenuated protein or mRNA levels of NF-kappa B/AP-1 target genes encoding TNF-alpha, IL-1 alpha, IL-6, and high-mobility group box-1 in vivo under endotoxemia or ALI. Finally, this study suggests IRAK4 as a molecular target of CGA in the treatment of innate immunity-related shock and organ dysfunction following insult of various TLR pathogens from bacteria and viruses.</P>

조리유형별 메뉴의 노동강도 측정에 관한 연구

백승희,양일선,김효정 한국조리과학회 2004 한국식품조리과학회지 Vol.20 No.4

The purpose of this study was to measure the labor intensity of menus according to various cooking types. Through a literature review and in-depth interview, the attributes that affected the labor intensity were identified as the level of skill, amount of effort, degree of tiredness, time consumed, and machine usage. A survey was conducted in April, 2001 among cooks who knew the entire process of cooking. There was a strong positive correlation between labor intensity and labor intensity attributes. Through regression analysis, a regression equation was obtained between labor intensity and labor intensity attributes. The labor intensity index calculated from this study showed the extent of labor intensity of menus. The result of this study could be used as basic data for foodservice managers to establish a menu planning and work schedule based on a scientific method.

노인 인구에서 신경인지기능저하와 혈청 지질농도와의 상관성

유영선,최석주,정성수,김지은,윤성욱,전동욱,백준형,박성우,이정구,추일한,김영훈 大韓神經精神醫學會 2008 신경정신의학 Vol.47 No.6

Objectives : In this study, the authors evaluated the correlation between eurocognitive impairments and serum lipids levels among Korean elderly over the age of 65. Methods : A total of 609 elderly individuals participated in this study. Screening for cognitive impairments were carried out using the Mini-Mental Status Examination-Korean version (MMSE-KC). There were 197 subjects above 1.5SD Of MMSE- KC and they were evaluated using the Korean versions of the Consortium to Establish a Registry for Alzheimer's Disease (AD) (CERAD-KC) and Geriatric Depression Scale (GDS-K). Results : There was a correlation between old age/low levels of education and AD (p<0.05, P<0.01). There was an inverse correlation between the serum level of total cholesterol and the word list recognition test scores. The serum levels of LDL cholesterol were inversely correlated with the scores on the constructional praxis test, word list recall test and word list recognition test. Inverse correlations between the serum level of triglyceride and scores on the word list recall test and word list recognition test were also observed. Conclusion : There were inverse correlations between the serum levels of lipids and language/memory function in subjects with AD.

석탄회로 합성한 제올라이트에 대한 암모니아성 질소 흡착특성 조사

류완호,이원묵,백일현,배장순 한국화학공학회 2003 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.41 No.4

국내 석탄화력 발전소에서 폐기되는 석탄회를 이용하여 폐수 중 암모니아성 질소 제거용 흡착제를 제조하고자 NaOH를 반응물로 한 수열합성 반응을 이용, 제올라이트를 합성하였으며 제조된 제올라이트를 실제공정에 활용하기 위하여 흡착실험 및 공정모사를 수행하였다. 또한 흡착제를 구형으로 제조하여 암모니아성 질소의 등온 흡착 공정에 이용하였으며 이 결과 Langmuir식에 잘 일치함을 알 수 있었다. 고정층에서의 흡착 거동은 축 방향 분산흐름, 입자 내부에서의 표면 확산 및 Sips 흡착 등온식을 바탕으로 한 고정층 흡착모델의 주요 공정 변수에 대한 파과곡선을 잘 모사할 수 있음을 확인할 수 있었다. Zeolite was synthesized from coal fly ash produced by a domestic power plant and applied for the removal of ammonia from waste water. Zeolite was synthesized using a hydrothermal method involving an akaline reaction with NaOH, and adsorption experiments and simulations were conducted. Adsorption experiments with the pelletized spherical zeolite were carried out. The experimental data obtained from adsorption isotherms agreed well with the Langmuir equation. Also, most of the correlated results for the fixed bed model based on surface diffusion and Sips adsorption isotherms equation were consistent with the experimental data.

석탄회를 이용한 제올라이트의 합성과 중금속 흡착 특성

류완호,이원묵,홍필선,양천희,안재영,백일현,이병노 한국화학공학회 2003 Korean Chemical Engineering Research(HWAHAK KONGHA Vol.41 No.5

석탄회를 이용, 중금속 제거용 흡착제 제조를 목적으로 NaOH를 반응물로 한 수열합성 반응으로 제올라이트를 합성하였으며, 이에 대한 성능특성 및 중금속 흡착실험을 수행하였다. SiO₂와 Al₂O₃를 주성분으로 한 석탄회를 NaOH에 의한 수열합성 반응으로 폐수 중에 포함되어 있는 중금속에 대한 제거능력이 높은 제올라이트를 합성하고자 하였다. 따라서 NaOH 농도, 시간을 변화시키면서 제올라이트를 합성하여 실험한 결과 4 M-NaOH, 4시간에서 최적의 조업조건을 얻을 수 있었다. 산에 의한 전처리 과정을 거친 합성 제올라이트는 pH 7-9.5로 중성을 나타내었다. 또한 산처리 합성 제올라이트를 이용하여 중금속인 P, Pb, Cd, Cr, Mn등의 흡착능을 비교한 결과 P, Pb, Cd 등은 비교적 흡착능이 우수하게 나타났지만 Cr과 Mn 등은 pH가 너무 높기 때문에 거의 흡착이 이루어지지 않았다. Zeolite was synthesized from coal fly ash produced by a domestic power plant and has applications in the removal of heavy metal from waste water. Zeolite was synthesized using a hydrothermal method involving an alkaline reaction with NaOH. The NaOH concentration and reaction times were varied in order to synthesize zeolite showing the maximum removal efficiency of heavy metal from waste water. The synthesis conditions were optimized at the concentration of 4M-NaOH and the reaction time of 4hn. The synthesized zeolite needed washing with HCI solution to improve the removal efficiency of P, Pb. Cd. Cr. Mn and it was maximized at pH 7-9.5 in leaching solution of synthesized zeolite.