Association of DOCK8, IL17RA, and KLK12 Polymorphisms with Atopic Dermatitis in Koreans

( Won Il Heo ),( Kui Young Park ),( Mi-kyung Lee ),( Yu Jeong Bae ),( Nam Ju Moon ),( Seong Jun Seo ) 대한피부과학회 2020 Annals of Dermatology Vol.32 No.3

Background: Early-onset and severe atopic dermatitis (AD) in patients increase the probability of the development of allergic rhinitis or asthma. Treatment and prevention strategies in infants and young children with AD are targeted toward treating the symptoms, restoring skin barrier functions, and reducing the absorption of environmental allergens in an attempt to attenuate or block the onset of asthma and food allergy. Objective: Given that the initiating events in AD remain poorly understood, identifying those at risk and implementing strategies to prevent AD is necessary. Methods: Whole-exome sequencing (WES) was performed in a 43 control group and a disease group with 20 AD patients without atopic march (AM) and 20 with AM. Sanger sequencing was carried out to validate found variants in cohorts. Results: DOCK8, IL17RA, and KLK12 single-nucleotide polymorphisms were identified by WES as missense mutations: c.1289C>A, p.P97T (rs529208); c.1685C>A, p.P562G (rs12484684); and c.457+27>C, rs3745540, respectively. A case-control study show that total immunoglobulin E (IgE) level was significantly increased in the AA genotype of DOCK8 compared to the CA genotype in allergic patients. The rs12484684 of IL17RA increased risk of adult-onset AD (odds ratio: 1.63) compared to the control for (A) allele frequency. AD and AM Patients with the IL17RA CA genotype also had elevated IgE levels. rs3745540 of KLK12 was associated with AD in dominant model (odds ratio: 2.86). Conclusion: DOCK8 (rs529208), IL17RA (rs12484684), and KLK12 (rs3745540), were identified using a new WES filtering method. the result suggests that polymorphism of DOCK8 and IL17RA might be related to increase the total IgE level. (Ann Dermatol 32(3) 197∼205, 2020)

Involvement of IL-10 gene promoter polymorphisms in the susceptibility for childhood asthma.

Kim, Kyung Won,Lee, Kyung Eun,Hong, Jung Yeon,Kim, Mi Na,Heo, Won Il,Sohn, Myung Hyun,Kim, Kyu-Earn Springer International 2011 Lung Vol.189 No.5

<P>Asthma and atopy have a complex background that may result from the interaction of genes and the environment. Interleukin (IL)-10 is known to play various roles in immune-regulating and anti-inflammatory responses. The aim of this study was to evaluate the possible effect of the IL-10 promoter polymorphisms on susceptibility to childhood asthma. We recruited 333 patients with atopic asthma, 55 with nonatopic asthma, and 248 normal controls. We performed a genetic association study of three genetic polymorphisms (IL-10 -1082A>G, IL-10 -819T>C, and IL-10 -592A>C) of the IL-10 promoter. There was no difference between atopic asthma, nonatopic asthma, and normal controls with respect to allele, genotype, or haplotype frequencies of these IL-10 polymorphisms. However, the -1082A>G polymorphism and ATA haplotype in the IL-10 promoter gene were associated with airway hyper responsiveness (AHR) and the -819T>C, -592A>C, and ATA and ACC haplotypes were also shown to be related to serum eosinophil cationic protein (ECP). Our results suggest that the polymorphisms within the IL-10 promoter may have a disease-modifying effect in the asthmatic airway.</P>

위암에서 Helicobacter pylori cagA, vacA, iceA 유전자와 숙주 Interleukin-1β및 Interleukin-1 수용체 길항제 유전자 다형성

이성훈 ( Seong Hun Lee ),김태오 ( Tae Oh Kim ),이동현 ( Dong Hyun Lee ),박원일 ( Won Il Park ),김광하 ( Gwang Ha Kim ),허정 ( Jeong Heo ),강대환 ( Dae Hwan Kang ),송근암 ( Geun Am Song ),조몽 ( Mong Cho ) 대한내과학회 2006 대한내과학회지 Vol.71 No.1

Background: Both Helicobacter pylori (H. pylori) cagA, vacA, iceA genotype and host IL-1B/IL-1RN polymorphisms play a role in determining the clinical consequences of H. pylori infection. This study aimed to investigate whether there might be any combinations of H. pylori cagA, vacA, iceA genotype and host IL-1B/IL-1RN polymorphisms that are particularly associated with the occurrence of gastric carcinoma in Korean patients. Methods: This study population was comprised of 239 patients with H. pylori infection: 122 with gastric carcinoma and 117 with gastritis only. DNA was isolated from gastric biopsy sample and H. pylori cagA, vacA and iceA genotype were determined by PCR. IL-1B-511 polymorphisms were genotyped by PCR-RFLP and IL-1RN polymorphisms were analyzed with variable number of tandom repeat after PCR. Results: H. pylori cagA, vacA, and iceA genotype were not associated with an increased risk for gastric carcinoma. IL-1B-511*T carriers and IL-1RN*2 carriers did not show increased risk for gastric carcinoma. On combination of bacterial/host genotypes, cagA+/IL-1B-511*T carriers and cagA+/IL-1RN*2 carriers, vacA s1/IL-1B-511*T carriers, vacA s1/IL-1RN*2 carriers, vacA m1/IL-1B-511*T carriers, vacA m1/IL-1RN*2 carriers, iceA1/IL-1B-511*T carriers, iceA1/IL-1RN*2 carriers showed no increased risk of gastric carcinoma. Conclusions: Combined H. pylori cagA, vacA, iceA genotype and host IL-1B/IL-1RN polymorphisms shows no increased risk of gastric carcinoma. Therefore, it seems other endogenous or exogenous factors may play more important role in the development of gastric carcinoma in Korean.(Korean J Med 71:24-37, 2006)

8주간의 유산소성 체조활동을 통한 뇌병변 장애인의 체력 및 염증반응지표 변화

허금 ( Keum Heo ),김광준 ( Kwang Jun KIm ),김권일 ( Kwon Il Kim ),박동호 ( Dong Ho Park ),전태원 ( Tae Won Jun ),송욱 ( Wook Song ) 한국특수체육학회 2009 한국특수체육학회지 Vol.17 No.4

본 연구의 목적은 뇌병변 장애인을 대상으로 8주간의 유산소성 체조활동을 실시하여 신체조성, 체력 및 염증반응지표의 변화에 대하여 알아보는 것이다. 본 연구의 피험자는남·녀 뇌병변장애 중 대표적인 뇌졸중 장애인 17명을 대상으로 시작되었지만 9명이 중도포기하여 최종 8명이 참가하였다. 운동 프로그램 참여 전 사전 검사를 실시하였으며, 기본적 변인으로 신장, 체중, Body Mass Index(BMI), 안정시 심박수, 안정시 혈압을 측정하고, 체력 변인으로는 체간 굴곡과 신전, 견관절 굴곡과 신전의 유연성과 악력을 통한근력, 폐활량을 통한 폐기능을 측정하였다. 또한 혈액성분으로는 혈중지질, 그리고 심혈 관질환 위험인자인 염증반응지표로서 C-reactive protein(CRP), Interleukin-6(IL-6), Tumor Necrosis Factor-α(TNF-α)를 분석하였다. 8주 유산소성 체조활동 프로그램은 매회50분씩 주 2회 실시하였으며, 운동강도는 운동자각도(RPE) 수준 13으로 유지하였다. 뇌병변 장애인의 유산소성 체조활동 프로그램 참여 후 운동의 효과를 검증한 결과 전체 집단에서 안정시 수축기혈압과 이완기혈압이 유의하게 감소하였다(p<.01). 또한 체력 요인에서는 체간 굴곡과 신전(p<.05), 건측의 견관절 굴곡과 신전(p<.01), 환측의 견관절 굴곡(p<.05)이 유의하게 증가하였다. 혈액 성분의 분석 결과 혈중지질에는 유의한 변화가 나타나지 않았으며, 염증반응지표의 경우 IL-6가 유의하게 감소하였고(p<.05), 유의하지는 않으나 CRP도 감소하는 경향을 나타냈다(p<.088). 결론적으로, 지속적이고 규칙적인 유산소성 체조활동은 뇌병변 장애인의 안정시 심박수와 혈압 및 체력을 개선시키는 효과가 있을 뿐만 아니라 심혈관질환의 위험요소로 알려져 있는 염증반응지표를 개선하는 데에도 긍정적인 영향을 주는 것으로 나타났다. The purpose of this study was to analysis the effect of aerobic gymnastic exercise for eight weeks on physical fitness and inflammatory markers which are known as risk factors for cardiovascular diseases in hemiplegic disabled after cerebral stroke. For this purpose, stroke patients(n=8) participated in aerobic exercise training 2 days/week, 50 mins/day, for 8 weeks and maintained at 13 level of RPE. Body composition, resting heart rate and blood pressure were measured before physical fitness test. Trunk flexion/extension, shoulder flexion/extension, grip strength, pulmonary function were measured as physical fitness test. Blood sample of 15ml was drawn from antecubital veins for measuring inflammatory markers(c-reactive protein, interleukin-6, tumor necrosis factor-α). The result of this study is as follows: Resting blood pressure decreased significantly after 8-week aerobic exercise training in total stroke patients (p<.01). After completion of the aerobic exercise program, trunk extension/flexion(p<.05), shoulder extension/fexion(p<.01), were significantly improved in total stroke patients. There was no significant improvement on blood lipid profiles in total stroke patients. However, IL-6 was significantly improved in stroke patients after 8-week aerobic exercise(p<.05). In conclusion, These findings suggests that regular aerobic gymnastic exercise decreases resting heart rate and blood pressure, and improves physical fitness, inflammatory markers which are known as a risk factor of cardiovascular diseases in person with disability occurred due to hemiparetic stroke

The Role of Collagen VI α6 Chain Gene in Atopic Dermatitis

( Hye Jung Jung ),( Won Il Heo ),( Kui Young Park ),( Mi-kyung Lee ),( Ji Young Ahn ),( Mi Youn Park ),( Seong Jun Seo ) 대한피부과학회 2022 Annals of Dermatology Vol.34 No.1

Background: In a previous study, we carried out whole-exome sequencing to identify genetic variants associated with early onset atopic dermatitis (AD) in Koreans and found that collagen VI α6 chain (COL6A6) gene polymorphisms are associated. COL6A6 is one of the chains that makes up the triple helix of collagen VI, and little is known about its role in AD. Objective: To identify how COL6A6 changes in AD and clarify its role. Methods: Immunohistochemical staining for COL6A6 was performed on tissues of AD, other skin diseases, and healthy controls. Human keratinocytes and fibroblasts were exposed to inflammatory cytokines and cultured to evaluate changes in COL6A6 expression. COL6A6 small interfering RNA (siRNA) was transfected into cells to identify the role of COL6A6. Results: Total COL6A6 mRNA was higher in AD than in controls. In AD tissues, COL6A6 mRNA decreased significantly in the epidermis compared to controls, whereas COL6A6 protein was increased in the dermis. In the cultured cells, COL6A6 mRNA was suppressed in the epidermis by interleukin (IL)-4 and IL-13, whereas COL6A6 protein was induced in the dermis. In the COL6A6 siRNA-transfected keratinocyte, mRNA of FLG, LOR, and CASP14 decreased compared to controls; in contrast, mRNA of MMP1 increased. Conclusion: The reduction of epidermal COL6A6 due to the genetic mutation can cause skin barrier damage and it can contributes to the early onset of AD. COL6A6 is induced by IL-4 and IL-13, and it may play a role in fibrotic remodeling and inflammatory processes, which are major features of AD.

Genetic polymorphism of DOCK8, IL17RA and KLK12 in Koreans with atopic dermatitis and allergic march

( Hye Sung Han ),( Jae Min Kim ),( Won Il Heo ),( Kui Young Park ),( Mi-kyung Lee ),( Seong Jun Seo ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

Background: Atopic dermatitis (AD) is one of the most common childhood diseases and has a complex etiology involving genetic and environmental factors. Thus, a broad understanding of genetic background is needed for early diagnosis of AD. Objectives: The purpose of this study was to identify of novel candidate functional genetic variants in Koreans with atopic dermatitis and allergic march. Methods: Whole-exome sequencing (WES) was performed in 20 AD and 20 AM Korean patients, and 40 Korean personal genome project (KPGP) controls. Sanger sequencing was carried out to validate found variants in 86 AD, 72 AM patients and 81 controls. Results: Three candidate variants of DOCK8 (rs529208), IL17RA (rs1248468), and KLK12 (rs3745540) were identified. rs529208 had no correlation with the development of AD but the AA genotype of DOCK8 had significantly increased total IgE level. rs1248468 had significantly increased risk of AD and the CA genotype of IL17RA had also increased total IgE level. rs3745540 was significantly associated with AD. Conclusion: DOCK8 (rs529208), IL17RA (rs1248468) and KLK12 (rs3745540) were deemed functionally interesting based on WES. Our case-control study suggests that the three variants detected in WES may enhance the risk of AD.

Pulmonary inflammation caused by silica dioxide nanoparticles in mice via TXNIP/NLRP3 signaling pathway

Je‑Oh Lim,Je‑Won Ko,Tae‑Yang Jung,Woong‑Il Kim,So‑Won Pak,In‑Sik Shin,Won‑Kee Yun,Hyoung‑Chin Kim,Jeong‑Doo Heo,Jong‑Choon Kim 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.3

Background Silica dioxide nanoparticles (SiONPs) have been used for various medical applications, including therapeutics and imaging, and the use of SiONPs has increased gradually over the years. However, despite an increase in the use of SiONPs, not much is known about mechanism of action of SiONPs and their pulmonary toxicity. Objective The present study investigated the pulmonary toxicity of SiONPs and explored the underlying mechanism of action, primarily focusing on thioredoxin-interacting protein (TXNIP)/NOD-like receptor pyrin domain-containing 3 (NLRP3) in SiONPs-treated mice. We investigated the toxic effects of SiONPs in the lung of BALB/c mice administered 5, 10, and 20 mg/kg SiONPs for 3 days. Results Exposure to SiONPs markedly increased inflammatory cell counts, including those of neutrophils and macrophages, and levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in a dose-dependent manner in the bronchoalveolar lavage fluid. Moreover, the inflammation was verified upon histopathological analysis. In addition, exposure to SiONPs increased the expression of TXNIP in a dose-dependent manner and, in turn, upregulated NLRP3 inflammasome proteins, which subsequently induced IL-1β production. Conclusion Collectively, exposure to SiONPs induced inflammation in the lungs of mice, which resulted in the activation of IL-1β production via the TXNIP-NLRP3 axis. Our results provide useful information on the pulmonary toxicity induced by SiONPs and provide insights into the underlying mechanism of action.

Anti-inflammatory effect of Apo-9′-fucoxanthinone via inhibition of MAPKs and NF-kB signaling pathway in LPS-stimulated RAW 264.7 macrophages and zebrafish model

Kim, Eun-A,Kim, Seo-Young,Ye, Bo-Ram,Kim, Junseong,Ko, Seok-Chun,Lee, Won Woo,Kim, Kil-Nam,Choi, Il-Whan,Jung, Won-Kyo,Heo, Soo-Jin Elsevier 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.59 No.-

<P><B>Abstract</B></P> <P>In this study, we confirmed the anti-inflammatory effect of Apo-9-fucoxanthinone (AF) in <I>in vitro</I> RAW 264.7 cells and <I>in vivo</I> zebrafish model. In lipopolysaccharide (LPS)-stimulated zebrafish, AF significantly decreased the production of reactive oxygen species (ROS), nitric oxide (NO) and cell death. In addition, the mRNA expression of inducible nitric oxide synthase (iNOS), suppressed cyclooxygenase-2 (COX-2) and an inflammatory cytokines; IL-1β, TNF-α were shown reduction. And AF significantly inhibited NO production and expression of iNOS in LPS-stimulated RAW 264.7 cells. Further, AF suppressed COX-2, prostaglandin E2 (PGE<SUB>2</SUB>), and pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) at 25, 50 and 100 μg/mL, respectively. Further mechanistic studies showed that AF suppressed the nuclear factor-kB (NF-kB) pathway and phosphorylation of mitogen-activated protein kinase (MAPK) pathway molecules such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). According to the results, AF can be used and applied as a useful anti-inflammatory agent of nutraceutical or pharmaceutical.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Anti-inflammatory effect of Apo-9-fucoxanthinone in <I>in vitro</I> RAW 264.7 cells and <I>in vivo</I> zebrafish </LI> <LI> Apo-9-fucoxanthinone suppressed NO production through NF-kB and MAPKs pathway. </LI> <LI> In LPS-stimulated zebrafish, Apo-9-fucoxanthinone significantly decreased ROS, NO, cell death and pro-inflammatory cytokines. </LI> <LI> Apo-9-fucoxanthinone can be extremely useful as an effective anti-inflammatory agent. </LI> </UL> </P>

다이아몬드휠을 사용한 WC-Co재의 고능률적 평면 연삭 가공에 관한 연구

김원일,허성중,강재훈,이재경 慶南大學校 附設 工業技術硏究所 1992 硏究論文集 Vol.10 No.-

WC-Co재는 금형 제작용으로 근래 그 사용이 급증하고 있다. 본 논문은 WC-Co재의 고능률 최적 연삭조건을 정립하기 위하여 연삭저항과 연삭비를 중심으로 실험적 연구를 행한 결과 다음과 같은 결론을 얻을 수 있었다. 1)WC-Co재의 가공에 대한 연삭저항은 연삭 깊이가 증가하고 다이야 몬드 연삭 숫돌의 주속도가 느릴수록, 공작물 연삭 속도가 감소할 수록 증가하였다. 2)WC-Co재의 경우, 연삭비는 테이블 이송 속도등의 증가와 더불어 감소함을 나타내었다. Recently, the making of WC-Co materials which are used for metallic mould is growing very rapidly. This investigation examines the grinding force and grinding ratio caused by experimental machining of WC-Co for research high efficiently optimal grinding condition. From the result of experiments obtained hear are summarized as follows and so forth. 1) For working WC-Co materials, the grinding force increases according to increase of depth of cut, decrease of surface velocity of diamond abrasive wheel and increase of surface velocity of work. 2) In case of WC-Co materials, grinding ratio is decrease according to increase of table feed rate et, al.

고품위 연삭 가공기법을 이용한 알루미나 세라믹스 부품의 강도향상에 관한 연구

김원일,강재훈,이재경,허성중 경남대학교 신소재연구소 1992 論文集 Vol.2 No.-

초지립 연삭 공구인 다이아몬드 휠을 사용하여 엔지니어링 세라믹스를 제거가공함에 있어 공구의 마멸 및 가공면 상의 가공 결함 등에 의한 강도 저하 현상 등이 야기되어지고 있다. 한편, 최적 절인 형성을 위한 가공 공정상의 빈번한 재드레싱 시간 등의 소요는 생산성 향상의 측면에 있어 장애가 되고 있다. 연삭 가공중의 연속 드레싱 기구를 고려해 봄으로써 계속적인 다이아몬드 지립의 양호한 절인 상태를 유지하며 고능률적으로 제거 가공을 추진하고, 절인 마멸에 의한 가공 결함 들을 극소화시키는 효과를 얻고자 실험적으로 본 연구를 수행하였다. 굽힘 강도 시편을 가공 제작하여 기계적 특성치의 변화를 구해봄으로써 이에 대한 재고찰을 해보았으며, 고품위 연삭 기법에 의한 우수한 결과치들을 얻을 수 있었다. Engineering ceramics have some excellent properies as the material for the mechanical components. It is, however, very difficult to grind ceramics with high efficiency because of their high strength, hardness and brittleness. In this paper experiments are carried out to obtain the effect of In-process dressing to grind the engineering ceramies with high efficency. To save running time for dressing process and obtain restraint effect of diamond grain wear, In-process dressing system using WA stick type honing stone is proposed. Representative engineering ceramics, A1₂O₃, are ground with diamond wheel. Also bending strength test is carried out to check upward tendency of mecahnical properties as the result of machining defact restraint through the grinding machining method using "In- process dressing" process. Some results obtained in this study provide useful information to attain the high efficiency grinding and the high mechanical properties of engineering ceramics.