Genetic effect of <i>CCR3</i> and <i>IL5RA</i> gene polymorphisms on eosinophilia in asthmatic patients

Lee, June-Hyuk,Chang, Hun Soo,Kim, Ji Hyun,Park, Se-Min,Lee, Yong Mok,Uh, Soo Taek,Rhim, Taiyoun,Chung, Il Yup,Kim, Yong-Hoon,Park, Byung Lae,Park, Choon-Sik,Shin, Hyoung Doo Elsevier 2007 The journal of allergy and clinical immunology Vol.120 No.5

<P><B>Background</B></P><P>Eosinophilic infiltration and peripheral blood eosinophilia in asthma require the cooperation of eosinophil-specific cytokines and chemokines and their receptors.</P><P><B>Objective</B></P><P>We investigated the association of polymorphisms in <I>CCR3</I> and <I>IL5RA</I> with asthma susceptibility or peripheral blood eosinophilia and the effects of the polymorphisms on receptor expression.</P><P><B>Methods</B></P><P>Polymorphisms in <I>CCR3</I> and <I>IL5RA</I> were identified and genotyped in 576 asthmatic patients and 180 healthy control subjects. CCR3 and IL-5 receptor α (IL-5Rα) protein expression on eosinophils was measured by means of flow cytometry.</P><P><B>Results</B></P><P>Although polymorphisms in <I>CCR3</I> were not associated with asthma susceptibility, the <I>CCR3</I> haplotype <I>ht2</I> showed a negative gene dose effect on the eosinophil count (<I>P</I> = .003–.009). <I>IL5RA c.−5091G>A</I> was weakly associated with eosinophil count. The effects of <I>ht2</I> were greater when paired with <I>IL5RA c.−5091A</I> (<I>P</I> = .001–.002). CCR3 protein expression was higher on eosinophils of asthmatic patients without <I>ht2</I> than in those with <I>ht2</I>. Asthmatic patients with the <I>IL5RA c.−5091A</I> allele showed higher IL-5Rα expression than those who were homozygous for the G allele.</P><P><B>Conclusion</B></P><P>The genetic association between <I>CCR3</I> polymorphisms and the number of circulating eosinophils was revealed as a novel finding. These associations were more pronounced when the <I>CCR3</I> polymorphisms were paired with polymorphisms in <I>IL5RA</I>. The protein expression levels of CCR3 and IL-5Rα on peripheral blood eosinophils are associated with the polymorphisms on their own genes.</P><P><B>Clinical implications</B></P><P>The identification of single nucleotide polymorphisms and haplotypes of <I>CCR3</I> and <I>IL5RA</I> might be useful in developing markers for intermediate phenotypes of eosinophil number and in designing strategies to control diseases related to hypereosinophilia.</P>

Chronological changes in inflammatory cytokines immunoreactivities in the mouse hippocampus after systemic administration of high dosage of tetanus toxin.

Yan, Bing Chun,Park, Joon Ha,Kim, In Hye,Shin, Bich Na,Ahn, Ji Hyeon,Yoo, Ki-Yeon,Lee, Deuk-Sik,Kim, Myong Jo,Kang, Il-Jun,Won, Moo-Ho Springer-Verlag 2012 Experimental brain research Vol.223 No.2

<P>Tetanus toxin (TeT) is an exotoxin and has a capacity for neuronal binding and internalization. In the present study, we compared changes in the immunoreactivities and protein levels of interleukin (IL-) 2 as a pro-inflammatory cytokine and IL-4 as an anti-inflammatory cytokine in the hippocampus proper (HP) and dentate gyrus (DG) after systemic treatment of 10 or 100?ng/kg TeT into mice. In this study, we could not find any neuronal damage or loss in any subregions of the hippocampus after TeT treatment. In the control groups, strong IL-2 immunoreactivity was shown in the stratum pyramidal (SP) of the HP and in the granule cell layer (GCL) of the DG. At 6?h post-treatment, IL-2 immunoreactivity was hardly detected in the SP and GCL; however, strong IL-2 immunoreactivity was shown in the stratum oriens of the HP in both the groups. Thereafter, intermediate IL-2 immunoreactivity was shown in the SP and GCL. On the other hand, intermediate IL-4 immunoreactivity was detected in the SP and GCL of the control groups. At 6?h post-treatment, IL-4 immunoreactivity in the SP and GCL was apparently increased. Thereafter, IL-4 immunoreactivity was lower than that at 6?h post-treatment. In brief, IL-2 and 4 immunoreactivities were easily detected in SP and GCL in the controls and dramatically decreased and increased at 6?h post-treatment, respectively.</P>

Protective effect of Silibinin on Silica Dioxide-induced inflammation through suppressing TXNIP/MAPKs/AP-1 signaling

Woong-Il Kim,Je-Oh Lim,Se-jin Lee,So-Won Pak,In-Sik Shin,Jong-choon Kim 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Silica dioxide nanoparticles (siONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinase (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP / MAPKs / AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, an this effect was closely related to the inhibition of TXNIP / MAPK/ AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.

<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. No.

<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>

골수이식 후 사이토카인과 골교체 생화학적표지자의 변화 및 상관관계

민우성,강무일,한제호,강성구,오기원,이원영,김혜수,문성대,손현식,신완식,김춘추,윤건호,차봉연,이광우,손호영 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.1

Background : Loss of bone mass is usually detected after BMT. The causes of bone loss are related with gonadal dysfunction and immunosuppressants. Cytokines, especially IL-6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study is to assess the relationship of bone turnover markers and cytokines of peripheral blood and bone marrow before and after allogeneic BMT. Methods : This prospective study included two analyses. The first was a study of 46 BMT recipients, examining the relationship between bone turnover markers and cytokines of serum which were measured before and 1, 2, 3, 4 week and 3 months after BMT. The second was a study of 14 BMT patients, measuring bone marrow plasma cytokines such as IL-6 and TNF-? at post-BMT 3 week and bone turnover marker at the same time to assess the relationship beween two parameters. Results : Serum ICTP, bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. There was positive correlation between serum ICTP and bone marrow IL-6 levels at the post-BMT 3 week with a statistical significance, but the correlation between bone turnover markers and bone marrow TNF-? or peripheral blood cytokines was not found. Conclusion : Our data suggest that the progressive increase of bone resorption after BMT is related with the increase of bone marrow IL-6, which is a potent stimulator of bone resorption in vivo(J Kor Soc Endocrinol 15:85-96, 2000).

Ahnak-knockout mice show susceptibility to Bartonella henselae infection because of CD4+ T cell inactivation and decreased cytokine secretion

( Eun Wha Choi ),( Hee Woo Lee ),( Jun Sik Lee ),( Il Yong Kim ),( Jae Hoon Shin ),( Je Kyung Se ) 생화학분자생물학회(구 한국생화학분자생물학회) 2019 BMB Reports Vol.52 No.4

The present study evaluated the role of AHNAK in Bartonella henselae infection. Mice were intraperitoneally inoculated with 2 × 10⁸ colony-forming units of B. henselae Houston-1 on day 0 and subsequently on day 10. Blood and tissue samples of the mice were collected 8 days after the final B. henselae injection. B. henselae infection in the liver of Ahnak-knockout and wild-type mice was confirmed by performing polymerase chain reaction, with Bartonella adhesion A as a marker. The proportion of B. henselaeinfected cells increased in the liver of the Ahnak-knockout mice. Granulomatous lesions, inflammatory cytokine levels, and liver enzyme levels were also higher in the liver of the Ahnak-knockout mice than in the liver of the wild-type mice, indicating that Ahnak deletion accelerated B. henselae infection. The proportion of CD4+interferon-y(IFN-y)⁺ and CD4⁺interleukin (IL)-4⁺ cells was significantly lower in the B. henselae-infected Ahnak-knockout mice than in the B. henselae-infected wild-type mice. In vitro stimulation with B. henselae significantly increased IFN-y and IL-4 secretion in the splenocytes obtained from the B. henselae-infected wild-type mice, but did not increase IFN-y and IL-4 secretion in the splenocytes obtained from the B. henselae-infected Ahnak-KO mice. In contrast, IL-1α, IL-1β, IL-6, IL-10, RANTES, and tumor necrosis factor-α secretion was significantly elevated in the splenocytes obtained from both B. henselae-infected wild-type and Ahnak-knockout mice. These results indicate that Ahnak deletion promotes B. henselae infection. Impaired IFN-y and IL-4 secretion in the Ahnak-knockout mice suggests the impairment of Th1 and Th2 immunity in these mice. [BMB Reports 2019; 52(4): 289-294]

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.

수술-교정 치료 환자의 통제 소재

이신재,안석준,백승학,김태우,장영일,양원식,서정훈,남동석 대한치과교정학회 2002 대한치과교정학회지 Vol.32 No.4

교정치료와 악교정 수술을 필요로 하는 환자가 점증하는 현 시점에 비추어, 이에 대한 기술적인 측면의 발전과는 달리 수술-교정 치료 환자에 대한 정신사회학적 혹은 정신심리적 양상에 대한 객관적인 정보는 그리 많은 주목을 받는 편이 아니었다. 수술-교정치료는 과학적인 치료과정이긴 하지만, 어느 정도 심미적 혹은 예술적인 측면을 지니는 선택 치료의 면모를 지닌다. 그러므로 치료에 대한 환자의 주관적인 느낌은 치료 기술이나 치료의 의학적 성공 여부보다 더 큰 영향을 미칠 수 있다. 그러므로, 수술-교정 (혹은 교정) 치료에 대한 환자의 반응을 예측하기 위한 정신심리적인 정보는 치료에 유용한 지표가 될 수 있다고 가정할 수 있다. 통제 소재에 대한 연구는 인간의 다양한 행동을 예측하기 위한 유용한 지표로 알려져 왔는데, 본 연구에서는 42명의 수술-교정치료 환자와 성별/연령별로 표본 추출된 42명의 통상적 교정치료 환자를 대상으로 삼아 정신=심리적 비교 및 분석의 방법으로 두 가지 종류의 내외 통제 소재(internal/external locus of control) 검사를 시행하였다. 그 결과 수술-교정치료군에서만 남자가 여자에 비하여 낮은 외적 통제(높은 내적 통제)의 경향을 보였다. 결론적으로 수술-교정치료 환자의 정신심리적 기반은 성형 수술 환자와는 달리 교정치료 환자와 유사한 경향을 지닌 것으로 생각되었다. Surgical-orthodontic treatment is an increasingly more common dental procedure whose unique psycho-social or psychological feature has not been fairly quantified objectively. Since the treatment of a surgical-orthodontic (or orthodontic) patient is part science and part art, a subjective recognition of a patient about his or her own treatment may be more important than technical success during and after treatment. Therefore, the knowledge of the patient''s underlying psychological status could be useful in the prediction of patient's response to surgical-orthodontic (or orthodontic) treatment. The purpose of this study was to investigate and evaluate the psychological difference between conventional orthodontic patient and surgical-orthodontic patient by using locus of control (LOC) examination. Locus of control scale has been proven to be extremely useful in the prediction of a variety of human behaviors. Two types of locus of control data (I-score, Internal locus of control score ; E-score, External locus of control score) were obtained for 42 surgical-orthodontic patients and randomly selected 42 conventional orthodontic patients (as a control group) matched for age and gender. No statistically significant difference was observed in the scale of internal and external locus of control between the groups of surgical-orthodontic patients, males showed lower E-score (external locus of control score, higher internal locus of control tendency) than females. The results of this study suggested that the psychological background of surgical-orthodontic patients, in contrast with that of cosmetic surgery patients, has a similar disposition with that of orthodontic patients.

주정중독 환자와 정상음주자에 대한 감정상태와 자기 지각, 가정환경, 사회적 지지에 관한 비교 연구

이정식,한광수,이유상,한일우,신용구 용인정신의학연구소 1997 용인정신의학보 Vol.4 No.1

3D 온라인 슈팅 게임 개발 : "3D 포트리스"

金敬植,崔勝寬,寓昔珍,申一卿,朴勝浩,李東熙,李東建,張孝善 호서대학교 공업기술연구소 2000 工業技術硏究所論文集 Vol.19 No.-

In this paper, features and efficiencies of the 3D engine are described which has been developed through the research of 3D real time rendering techniques. And an on-line shooting game "3D Fortress" which has been developed using this 3D engine with server technologies is introduced for the techniques and methodology applied in the process of development of the game as well as the features and discussions of its implementation.