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)

<i>In vivo</i> genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure

Kim, Jin Sik,Sung, Jae Hyuck,Choi, Byung Gil,Ryu, Hyeon Yeol,Song, Kyung Seuk,Shin, Jae Hoon,Lee, Jong Seong,Hwang, Joo Hwan,Lee, Ji Hyun,Lee, Gun Ho,Jeon, Kisoo,Ahn, Kang Ho,Yu, Il Je Informa Healthcare 2014 INHALATION TOXICOLOGY Vol.26 No.4

<P>Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells <I>in vivo</I>, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m<SUP>3</SUP>), low (0.17 mg/m<SUP>3</SUP>), middle (0.49 mg/m<SUP>3</SUP>), and high (0.96 mg/m<SUP>3</SUP>) dose group, and exposed to MWCNTs <I>via</I> nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (<I>p</I> < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (<I>p</I> < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H<SUB>2</SUB>O<SUB>2</SUB> levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (<I>p</I> < 0.05). Conversely, the female rats showed no changes in the H<SUB>2</SUB>O<SUB>2</SUB> levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.</P>

Threshold Rigidity Values for the Asbestos-like Pathogenicity of High-Aspect-Ratio Carbon Nanotubes in a Mouse Pleural Inflammation Model

Lee, Dong-Keun,Jeon, Soyeon,Han, Youngju,Kim, Sung-Hyun,Lee, Seonghan,Yu, Il Je,Song, Kyung Seuk,Kang, Aeyeon,Yun, Wan Soo,Kang, Sung-Min,Huh, Yun Suk,Cho, Wan-Seob American Chemical Society 2018 ACS NANO Vol.12 No.11

<P>The qualitative and quantitative evaluation of the physicochemical parameters associated with the pathogenicity of high-aspect-ratio nanomaterials is important for comprehensive regulation efforts and safety-by-design approaches. Here, we report quantitative data on the correlations between the rigidity of these nanomaterials and toxicity endpoints <I>in vitro</I> and <I>in vivo</I>. As measured by new ISO standards published in 2017, rigidity shows a strong positive correlation with inflammogenic potential, as indicated by inflammatory cell counts and IL-1β (a biomarker for frustrated phagocytosis) levels in both the acute and chronic phases. <I>In vitro</I> experiments using differentiated THP-1 cells find that only highly rigid multiwalled carbon nanotubes (MWCNTs) and asbestos fibers lead to piercing and frustrated phagocytosis. Thus, this study suggests a bending ratio of 0.97 and a static bending persistence length of 1.08 as threshold rigidity values for asbestos-like pathogenicity. However, additional research using MWCNTs with rigidity values that lie between those of non-inflammogenic (<I>D</I><SUB>b</SUB> = 0.66 and SBPL = 0.87) and inflammogenic fibers (<I>D</I><SUB>b</SUB> = 0.97 and SBPL = 1.09) is required to identify more accurate threshold values, which would be useful for comprehensive regulation and safety-by-design approaches based on MWCNTs.</P> [FIG OMISSION]</BR>

Aberrant expression of interleukin-10 and activation-induced cytidine deaminase in B cells from patients with Behçet's disease

Yoon, Jeong-Yun,Lee, Yeojin,Yu, Seong-Lan,Yoon, Hee-Kyung,Park, Ha-Yan,Joung, Chung-Il,Park, Seok-Rae,Kwon, Mihye,Kang, Jaeku D.A. Spandidos 2017 Biomedical reports Vol.7 No.6

<P>Despite extensive studies, the pathogenesis of Behçet's disease (BD) remains unclear. In particular, the roles of B cells in patients with BD have not been elucidated. Activation-induced cytidine deaminase (AID) is a critical enzyme for immunoglobulin (Ig) heavy chain class switching and somatic hypermutation in B cells and the abnormal expression of AID in various immune conditions has previously been studied. B10 cells, an interleukin (IL)-10-secreting subset of regulatory B cells, function to downregulate inflammation and autoimmunity. Thus, in the present study, the relevance of B cells in patients with BD was investigated. The plasma levels of IL-10 and IgA and the proportions of cluster of differentiation (CD)43<SUP>+</SUP> B cells, excluding naïve B cells, were measured in 16 patients with BD and 16 age- and sex-matched healthy controls (HCs). Additionally, the mRNA levels of IL-10 and AID were assessed in B cells from fresh peripheral blood samples of the BD patients and HCs. The plasma level of IL-10 in patients with BD did not differ significantly from that in HCs. Similarly, there was no significant difference in the plasma level of IgA, although a slight increase was observed in patients with BD compared with that in HCs. There were no differences in CD43<SUP>+</SUP>CD19<SUP>+</SUP> B cell numbers between patients with BD and HCs. However, IL-10 mRNA levels were significantly reduced (P<0.05), while AID mRNA levels were significantly increased (P<0.01) in the B cells of patients with BD compared with those in HCs. These results provide insight into the role of B cells in patients with BD.</P>

Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells

Cho, Mi Suk,Park, Won Sun,Jung, Won-Kyo,Qian, Zhong-ji,Lee, Dae-Sung,Choi, Jung-Sik,Lee, Da-Young,Park, Sae-Gwang,Seo, Su-Kil,Kim, Hak-Ju,Won, Jun Yeon,Yu, Byeng Chul,Choi, Il-Whan Informa Healthcare USA, Inc. 2014 PHARMACEUTICAL BIOLOGY Vol.52 No.7

<P><I>Context</I>: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown.</P><P><I>Objective</I>: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells <I>in vitro</I>.</P><P><I>Materials and methods</I>: To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used.</P><P><I>Results</I>: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1β (4.775 versus 0.713 pg/ml, IC<SUB>50</SUB> = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC<SUB>50</SUB> = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC<SUB>50</SUB> = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation.</P><P><I>Discussion and conclusion</I>: Our results indicated that CAPE can modulate mast cell-mediated allergic disease.</P>

아토피 피부염 모델에 대한 β-1,3/1,6-glucan과 Lactobacillus plantarum LM1004의 면역 조절 효과

김인성(In Sung Kim),김성학(Sung Hak Kim),김정아(Jeong A Kim),유다윤(Da Yoon Yu),김광일(Gwang Il Kim),박동찬(Dong-Chan Park),임종민(Jong Min Lim),이상석(Sang Suk Lee),최인순(In Soon Choi),조광근(Kwang Keun Cho) 한국생명과학회 2018 생명과학회지 Vol.28 No.1

본 연구에서는 아토피 피부염 동물 모델에 대한 β-1,3/1,6-glucan과 L. plantarum LM1004의 면역조절 효과를 확인하고자 하였다. 가려움증의 횟수와 유출된 evans blue, 그리고 혈청 IgE와 histamine의 농도는 β-1,3/1,6-glucan과 L. plantarum LM1004를 섭취한 그룹에서 아토피 피부염 유발그룹에 비해 유의적으로 감소하는 결과를 나타내었다. 아토피 피부염이 유발되면 전사 수준에서 Th2 및 Th17 세포의 전사인자 및 cytokine은 과발현되며, β-1,3/1,6-glucan과 L. plantarum LM1004를 섭취하였을 때 이를 유의적으로 감소되었다. 또한 β-1,3/1,6-glucan과 L. plantarum LM1004는 Th1 및 Treg 세포의 전사인자(T-bet, GATA-3, RORγT, Foxp3) 및 cytokine (INF-γ, IL-4, IL-17, TGF-β)의 발현을 증가시킴으로써 면역 균형을 조절하는 것으로 나타났다. Galectin-9과 filaggrin은 아토피 피부염 유발 처리군에서 유의적으로 가장 낮았으며, β-1,3/1,6-glucan 처리군에서 유의적으로 가장 높게 나타났다. 이와 반대로 TSLP는 아토피 피부염 유발그룹에서 유의적으로 가장 높았으며 β-1,3/1,6-glucan과 L. plantarum LM1004를 섭취한 그룹은 대조군과 유사한 수준이었다. 이러한 결과를 통해 β-1,3/1,6-glucan과 L. plantarum LM1004는 아토피 피부염 동물 모델에서 면역조절 작용 및 아토피 피부염의 개선 효과를 가짐을 알 수 있었다. 따라서 β-1,3/1,6-glucan과 L. plantarum LM1004는 아토피 피부염에 유용한 천연소재로서 사용될 것으로 기대된다. In this study, we examined the efficacy of the immune regulation of β-1,3/1,6-glucan and Lactobacillus plantarum LM1004 on atopic dermatitis models. The oral administration of β-1,3/1,6-glucan and L. plantarum LM1004 on mice significantly decreased the amount of scratching, leakage to evans blue, and concentrations of serum immunoglobulin E (IgE) and histamine compared with the atopic dermatitis–induced group. When atopic dermatitis was induced, the transcription factors (GATA-3, retinoic acid-related orphan receptor γ T [RORγT]) and cytokines (interleukin-4 [IL-4], IL-17) of Th2 and Th17 cells were overexpressed at the transcriptional level, and they significantly decreased with oral administration of β-1,3/1,6-glucan and L. plantarum LM1004. In addition, β-1,3/1,6-glucan and L. plantarum LM1004 were shown to modulate the immune balance by increasing the expression of Th1 and Treg transcription (T-bet, forkhead box p3 [Foxp3]) and cytokines (interferon-γ [IFN-γ], transforming growth factor-β [TGF-β]). Galectin-9 and filaggrin were significantly lower in the atopic dermatitis–induced group and significantly higher in the β-1,3/1,6-glucan-treated group. In contrast, thymic stromal lymphopoietin (TSLP) was highest in the atopic dermatitis–induced group, while mice that were orally administered β-1,3/1,6-glucan and L. plantarum LM1004 showed similar TSLP levels to the control group. These results indicate that β-1,3/1,6-glucan and L. plantarum LM1004 have immunomodulatory effects and atopic dermatitis improvement effects in an animal model of atopic dermatitis. Therefore, it is expected that β-1,3/1,6-glucan and L. plantarum LM1004 can be used as natural materials in the treatment of atopic dermatitis.

영·유아 언어, 인지, 사회·정서 발달 평가도구 문항 개발을 위한 예비연구

이종숙,신은수,박은혜,김영태,유영의,최일선,유흥옥 이화여자대학교 교육과학연구소 2009 교육과학연구 Vol.40 No.3

본 연구는 만 2~5세 영·유아의 발달 상태를 객관적으로 평가함과 동시에 발달이 지연된 영·유아를 선별할 수 있는 발달평가도구 문항을 개발하기 위한 예비연구이다. 이를 위해 문헌고찰 및 발달관련 평가도구들을 비교 분석하여 발달지표를 선정하고, 만 2세~5세까지의 영·유아의 언어, 인지, 사회·정서발달영역을 교사관찰에 기초하여 평가할 수 있는 문항을 개발하였다. 연구대상은 대도시, 중소도시, 읍면 소재지 별로 표집 된 만 2세부터 5세까지 총 13개 유아교육기관에 다니는 435명의 영·유아들이며, 본 연구에서 최종 개발된 평가도구의 문항은 총 141문항이다. 평가도구 문항은 언어, 인지, 사회·정서발달영역별로 영·유아의 행동과 언어를 중심으로 교사가 관찰하고, 관찰하기 어려운 문항에 대해서는 단서와 kit를 제시하여 평가할 수 있도록 구성하였다. 개발된 평가도구 문항의 적절성을 알아보기 위하여 내용 타당도와 내적 신뢰도를 살펴본 결과 비교적 양호한 것으로 나타났다. This was a preliminary study to construct a developmental rating scale for understanding children's objective developmental levels and screening developmental disabilities. For this purpose, a developmental indicator was selected by a literature review and comparative analysis of related developmental assessment tests. An assessment scale based on teacher's observations to measure language, recognition, and social-emotional developmental areas was developed. The subjects were 435 young children aged 2 to 5 who lived in both urban and rural areas. A trial test consisted of 141 assessment items in the language, recognition, and social-emotional developmental domains. The developmental scale was evaluated by teachers who observed children's behavior and language, and used clues and kits. Tests on validity and reliability for confirming the appropriateness of the developed assessment scale showed that content was relatively valid and internally consistent.

超音波檢査를 利用한 排卵前後의 卵胞成長에 關한 硏究

李麗一 全南大醫大 1984 전남의대학술지 Vol.21 No.4

크론병에 대한 CoPPLX의 방어효과에 대한 연구

이호학,김유림,문창기,이재일,양병윤,김종수,이정민,정재혁,안석진,박상준,김윤권,김소연,김영중,조민구,최영자,장성조 圓光大學校 醫科學硏究所 2005 圓光醫科學 Vol.20 No.1

지능형 망 관리시스템 기반 구현을 위한 기본 모듈의 설계 및 규현

兪一圭,李充基 明知大學校 産業技術硏究所 2002 産業技術硏究所論文集 Vol.21 No.-

Most of network management system(NMS) depends on network manager, in order to monitor states of networks in realtime and locate, diagnose, and treat faults. The architecture of NMS and main algorithms are described, which enables actions for repeated fault diagnosis and treatment after analyzing states of networks intelligently and locating unusual symptoms of networks.