Retinoic acid enhances lactoferrin-induced IgA responses by increasing betaglycan expression

Lee, Jeong-Min,Jang, Young-Saeng,Jin, Bo-Ra,Kim, Sun-Jin,Kim, Hyeon-Jin,Kwon, Bo-Eun,Ko, Hyun-Jeong,Yoon, Sung-il,Lee, Geun-Shik,Kim, Woan-Sub,Seo, Goo-Young,Kim, Pyeung-Hyeun CHINESE SOCIETY OF IMMUNOLOGY 2016 CELLULAR AND MOLECULAR IMMUNOLOGY Vol.13 No.6

<P>Lactoferrin (LF) and retinoic acid (RA) are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan (transforming growth factor-beta receptor III, T beta RIII) and activation of canonical TGF-beta signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line alpha (GL alpha) transcription and GLa promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced T beta RIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 (CCR9) and alpha 4 beta 7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9(+)IgA(+) plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses.</P>

Retinoic acid induces expression of Ig germ line α transcript, an IgA isotype switching indicative, through retinoic acid receptor

Mi-Hee Park,박석래,Mi-Ra Lee,Young-Ha Kim,Pyeung-Hyeun Kim 한국유전학회 2011 Genes & Genomics Vol.33 No.1

Retinoic acid (RA) is considered to possess an activity of IgA isotype switching. Thus far, TGF-β1 is known to be the most powerful IgA isotype switch factor. To elucidate the molecular mechanisms underlying the Ig germ line (GL) α transcriptional regulation by RA, we constructed three different sizes of mouse GLα promoter reporters; short-GLα(-130/+14), middle-GLα(-448/+72) and long-GLα(-3028/+72). Based on luciferase assay, RA increased the activity of all three GLα promoter reporters by approximately 2-fold and the effect was further enhanced by TGF-β1. Overexpression of Smad3/4 increased TGF-β1-induced GLα promoter activities but had no effect on RA-induced GLα promoter activities. In order to analyze the characteristics of the RA-inducible GLα promoter region,we also constructed two mutant reporters: Smad3 binding elements (SBEs)-substituted short-GLα (short-GLα mSBE)and Runx3 binding elements (RBEs)-substituted short-GLα(short-GLα mRBE) promoter reporters. Promoter activities of the two mutant reporters to RA were comparable to that of wild type reporter, while those of the two mutant reporters to TGF-β1 were markedly diminished as compared to that of WT short-GLα. Finally, RA-induced GLα transcription was virtually disappeared by LE540, an antagonist of RA receptor (RAR). Taken together, these results suggest that RA induces GLα transcription mainly through RAR pathway, where neither Smad3/4 nor Runx3 is involved.

류마티스관절염 환자의 인슐린 저항성 결정인자

이정욱 ( Joung Wook Lee ),박영은 ( Young Eun Park ),조미라 ( Mi Ra Cho ),백승훈 ( Seung Hoon Baek ),김근태 ( Geun Tae Kim ),이준희 ( Jun Hee Lee ),김성일 ( Sung Il Kim ) 대한류마티스학회 2009 대한류마티스학회지 Vol.16 No.2

Objective: Rheumatoid arthritis (RA) is associated with an increased cardiovascular events. These may be related to insulin resistance (IR). We evaluated status of IR and analyzed the relationship between IR and clinical and laboratory characteristics in patients with RA. Methods: We examined 52 RA patients (43 females) and 52 age and sex matched healthy controls. We measured Homeostasis model assessment (HOMA) IR, calculated according to fasting serum glucose and insulin. Results: In patients, age was 50.8±10.2 years old, disease duration was 42.1±30.9 months. In controls, HOMA IR was 0.62±0.30 and in patients, it was 1.28±0.50. This difference was highly significant (p<0.001). Patients with early RA (disease duration is less than 36 months) were 28, and established RA (more than 36 months) were 24. HOMA IR was significantly higher in patients with established RA (1.42±0.45) than those with early RA (1.16±0.45) (p=0.03), and significantly correlated with disease duration (r=0.36, p=0.01), BMI (r=0.36, p<0.001), total cumulative prednisolon dose (r=0.34, p=0.01). Disease duration and BMI were independent predictors for HOMA IR (p<0.01, p=0.03). Conclusion: In patients with RA, IR measured by HOMA IR was more significantly increased than that of healthy control and significantly correlated with disease duration, BMI, and total cumulative prednisolon dose; however, the determinants of HOMA IR in RA patients were disease duration and BMI.

신소설 「血의 淚」에 대한 수사학적 접근-이항 대립에 의한 대조법을 중심으로-

이주라 ( Lee Ju-ra ) 한국어문학국제학술포럼 2005 Journal of Korean Culture Vol.7 No.-

In transition to modern ages, the old orders which once ruled Chosun dynasty lost their power, so various discourses for new orders struggled to possess the initiative position. Also the way of writing got rid itself from discipline of medieval grammar that it was once based on, and stared to obtain new compositions of discourses for order of changing world. And also newspapers of this era took a very important role to provide writers with opportunities to try and experiment brand new ways of writing. Newspapers tried to make new compositions of discourses in various artistic and non-artistic types of writing, such as sundry reports, essays, and stories. ‘Shin so-sul’ was made on this background in the era. Because of that, with criteria of modern novels which were established after the time that literature became professional work, ‘shin so-sul can be easily criticized as a premature style that the composition was naive and the writers’ intention was shown too directly. But ‘shin so-sul’ was not a professional writing style, but a new style invented to show the discourse of that era. So the approach to ‘shin so-sul’ should be made with analysis focused on its own compositions of discourses. For that reason, this paper will consider, through rhetorical method, how the era's discourse was composed < The Tears of Blood > by In-jik Lee, known as the first ‘shin so-sul’ was published on {Man-se Bo}. {Man-se Bo} was a bulletin newspaper of ‘Chun-do Kyo’ (a religion developed by Jae-woo Choi), and Lee was a chif editor and played a core role of it. He published many ‘shin so-sul’ like < The Tears of Blood >, < The Sound of Ghost >, and so forth on the bulletin. For him, ‘Shin so-sul’ was a method to teach readers the importance of education and development of knowledge. That’s why we can find out a special feature of transition to modern ages’ style of narrative from Lee’s composition of discourses of enlightenment and education in his works. The most significant rhetoric is antithesis. The antithesis in this work is based on dichotomy and negation. Lee presents a situation which is very familiar to the public reader, and presents a specific situation to make them two terms of a comparison. After that, he makes these two terms confrontational by denying the former and granting the latter. By comparison of general situation and specific situation, Lee emphasizes that the time was very different form the past. And by comparison of the characters, he distinguishes a special person with great ability from ordinary people. Also comparison of old tradition and modern civilization suggests a feature of new society which must be pursued by a self with new identity for new world. The antithesis used for compose the phrase, escalating into a method of narrative composition, emphasizes the discourse of enlightenment. Lee’s < The Tears of Blood > clearly presents the new world order must be chased by the society of the era and new possibility to alternate old things with new things, by comparing them. This antithesis shows that the era's rhetorical feature pursues the langage's transparency and also it plays a effective role to transmit the discourse of enlightenment.

Network Analysis을 이용한 류마티스관절염 활액 대식세포에서 유전자 발현 연구

지종대 ( Jong Dae Ji ),김태환 ( Tae Hwan Kim ),이빛나라 ( Bit Na Ra Lee ),최성재 ( Sung Jae Choi ),이영호 ( Young Ho Lee ),송관규 ( Gwan Gyu Song ) 대한류마티스학회 2011 대한류마티스학회지 Vol.18 No.2

Objective. We wanted to investigate the mechanisms that could account for the pathogenesis of rheumatoid arthritis, so we examined the different expressions of the genes in rheumatoid arthritis (RA) synovial fluid macrophages as compared with that of normal peripheral blood (PB) monocyte-derived macrophages using microarray and bioinformatic analysis. Methods. We examined the expression of genes by using a gene expression oligonucleotide microarray. The differences of the gene expressions between the RA synovial macrophages and the normal PB monocytes-derived macrophages were analyzed using bioinformatic tools, including cytoscape and its plugin. Results. In this study, we found that 899 genes (464 genes up-regulated and 435 genes down-regulated) were differentially expressed between the two groups. Among the 899 genes, 552 genes were included for gene ontology analysis and network analysis. Based on biological process ontology, they were categorised mainly into immune response processes, responses to stimulus and signaling and regulation of biological processes. In addition to the genes related with STAT1 and AP-1 signaling, we found that the genes involved in the antigen processing and the cell cycle are abundantly expressed in RA synovial macrophages, suggesting that these genes may play an important role in the pathogenesis of RA. Conclusion. Our study suggest that this approach using integration of the gene expression profile with the protein interaction data may help to find several important pathogenic mechanisms in RA.

정신분열병 환자에서 얼굴 영상의 작동기억 장애 : 기능자기공명영상연구

이창욱,김태석,주라형,박주미,박여진,김종진,전신수,배치운,김정진,이수정,이철,백인호 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.2

Objectives : Impaired processing of facial information is one of the broad ranges of cognitive deficits seen in patients with Schi-zophrenia. We aimed to elucidate the differences in brain activities involved in the process of facial working memory between schizophrenic patients and healthy comparison subjects. Methods : Twelve patients with schizophrenia were recruited along with twelve demographically matched healthy volunteers as a comparison group. Functional magnetic resonance imaging (fMRI) was used to assess cortical activities during the Perfor-mance of a 2-back working memory paradigm using images of neutral faces as mnemonic content. Rcsults : The patient group performed the tasks with reduced accuracy. Group analysis revealed that the left fusiform gyrus, the right superior frontal gyrus, the bilateral middle frontal gyri/insula, the left middle temporal gyrus, the precuneus, the quadrangular lobules and the vermis of cerebellum showed decreased cortical activities in the patient group. On the other hand, an increased level of activation in the lateral prefrontal cortex and the pahetal lobule was observed from the patient group, all in the right hemisphere. Conulusion : A decreased level of activity in the left fusiform gyrus among the patient group implicates inefficient processing of facial information. An increased level of activation in prefrontal and parietal neural networks from the patient group confirms earlier findings on the impaired working memory of patients with schizophrenia.

청각장애초등학생을 위한 음악교육프로그램 개발 연구

이드보라ㆍ남선화ㆍ정미라(Debora LeeㆍNam Sun WhaㆍJeong Mi ra) 한국특수교육학회 2016 특수교육학연구 Vol.50 No.4

<i>Vigna angularis</i> inhibits IL-6-induced cellular signalling and ameliorates collagen-induced arthritis

Oh, Hyun-Mee,Lee, Seung Woong,Yun, Bo Ra,Hwang, Byung Soon,Kim, So Nam,Park, Chan Sun,Jeoung, See-Hwa,Kim, Hyun-Kyu,Lee, Woo Song,Rho, Mun-Chual Oxford University Press 2014 Rheumatology Vol.53 No.1

<P><B>Objectives.</B> The present study was conducted in order to assess whether extracts or isolated compounds from <I>Vigna angularis</I> were able to suppress IL-6 signalling and to show the therapeutic effect on collagen-induced arthritis (CIA) in mice.</P><P><B>Methods.</B> The effect of <I>V. angularis</I> on IL-6 signalling was studied by measuring Stat3-dependent luciferase activity, expression of inflammation-related genes, and phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) induced by IL-6. CIA was induced by immunizing with bovine type II collagen. <I>V. angularis</I> extract (VAE) was administrated orally at 50 and 100 mg/kg from day 1 to day 28. Induction of arthritis was evaluated with a visual scoring system and histological analysis.</P><P><B>Results.</B> Extracts or two triterpenoid compounds from <I>V. angularis</I> showed potent inhibitory effects on pSTAT3-inducible luciferase activity, STAT3 tyrosine phosphorylation and the expression of inflammation-related genes induced by IL-6. Administration of VAE significantly suppressed the progression of CIA, accompanied by a reduced antibody response to type II collagen and protection from tissue damage in knee joints.</P><P><B>Conclusion.</B> Administration of VAE has a therapeutic effect on CIA and this effect is associated with the inhibitory activity on IL-6/STAT3 signalling. These results suggest that extracts or compounds from <I>V. angularis</I> could be a useful treatment for diseases related to IL-6, including RA.</P>

Poster Session : PS 0691 ; Rheumatology ; A Randomized, Double-Blind, Phase 3 Equivalence Trial Comparing the Etanercept Biosimilar, Hd203, to Reference Etanercept, in Combination with Methotrexate (MTX) in Korean Patients with Rheumatoid Arthritis (RA)

( Sang Cheol Bae ),( Jinseok Kim ),( Jung Yoon Choe ),( Won Park ),( So Ra Lee ),( Yong Ho Ahn ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background: Etanercept is a recombinant fusion protein that blocks TNF. HD203 is a biosimilar of etanercept with demonstrated comparability across pharmacokinetics, safety and tolerability. The objectives of this study were to evaluate equivalence in effi cacy and compare safety of HD203 with reference etanercept, in combination with MTX in patients with RA. (ClinicalTrials. gov NCT01270997). Methods: Korean patients (male or female aged =20 years) with active RA were randomized (1:1) to 25 mg HD203 or reference etanercept, administered subcutaneously twice weekly with MTX for 48 weeks. The primary endpoint was the proportion of patients achieving ACR20 at week 24. Secondary endpoints included ACRn, DAS28, andEULAR response at week 24 and 48, safety and immunogenicity. Results: In total, 294 patients were randomized: HD203, n=147; reference etanercept, n=147. The proportion of patients achieving ACR20 at week 24 was not signifi cantly different between HD203 and reference etanercept. Equivalent effi cacy was demonstrated within predefined margins. There were no significant differences between proportions achieving ACR20 at week 12 and 48. ACR50 and ACR70 displayed similar trends. There were no signifi cant differences between groups for ACRn, DAS28, and EULAR response. Safety set analysis (HD203, n=147; reference etanercept, n=146) revealed no signifi cant difference for treatment-emergent (all-causality) adverse events (AEs): HD203 76. 87% vs. reference etanercept 78. 08% (p=0. 8040). No significant differences between HD203 and reference etanercept were observed for adverse drug reactions, serious AEs, or discontinuations due to AEs. Few patients tested positive for anti-drug antibodies. Conclusions: The study met the primary endpoint of demonstrating equivalent effi cacy of HD203 compared to reference etanercept. HD203 was well tolerated, with a safety profi le comparable to reference etanercept in this population of patients with RA.

A phase III, multicentre, randomised, double-blind, active-controlled, parallel-group trial comparing safety and efficacy of HD203, with innovator etanercept, in combination with methotrexate, in patients with rheumatoid arthritis: the HERA study

Bae, Sang-Cheol,Kim, Jinseok,Choe, Jung-Yoon,Park, Won,Lee, Sang-Heon,Park, Yong-Beom,Shim, Seung-Cheol,Lee, Shin-Seok,Sung, Yoon-Kyoung,Choi, Chan-Bum,Lee, So-Ra,Park, HanYu,Ahn, Yongho H. K. Lewis 2017 Annals of the rheumatic diseases Vol.76 No.1

<P>Conclusion The study met the primary objective of demonstrating equivalent efficacy of HD203 and ETN. HD203 was well tolerated, with safety comparable with ETN in this population of patients with RA.</P>