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>

The Correlation of Serum IL-12B Expression With Disease Activity in Patients With Inflammatory Bowel Disease

Lee, Hye Won,Chung, Sook Hee,Moon, Chang Mo,Che, Xiumei,Kim, Seung Won,Park, Soo Jung,Hong, Sung Pil,Kim, Tae Il,Kim, Won Ho,Cheon, Jae Hee Williams & Wilkins Co 2016 Medicine Vol.95 No.23

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>Genetic variants in <I>IL12B</I>, encoding the p40 subunit common in interleukin-12 (IL-12) and interleukin-23, were identified as the susceptibility loci for inflammatory bowel disease (IBD). This study aimed to identify the correlation of serum IL-12B expression with disease activity in patients with IBD and evaluate the possibility of IL-12B as a biomarker for assessing inflammatory status in IBD.</P><P>A total of 102 patients with IBD, including 38, 32, and 32 patients with Crohn's disease (CD), ulcerative colitis (UC), and intestinal Behçet's disease (intestinal BD), respectively, were included. The clinical and laboratory data from the patients were collected at the time of serum IL-12B measurement. Serum IL-12B levels were measured using an enzyme-linked immunosorbent assay.</P><P>The median IL-12B levels in patients with CD, UC, and intestinal BD were significantly higher than those in controls (1.87, 2.74, and 2.73 pg/mL, respectively, vs. 1.42 pg/mL, all <I>P</I> <0.05). IL-12B concentrations were associated with disease activity in patients with UC and intestinal BD but not in those with CD. IL-12B levels were increased with increasing disease activity in patients with UC (<I>P</I> <0.001). Likewise, patients with active intestinal BD had higher IL-12B levels than those without active disease (<I>P</I> = 0.008). IL-12B levels were correlated with the endoscopic disease activity of UC (<I>P</I> = 0.002) and intestinal BD (<I>P</I> = 0.001) but not that of CD.</P><P>Serum IL-12B levels were significantly correlated with clinical and endoscopic disease activity in patients with UC and intestinal BD, suggesting its potential use as a biomarker for assessing disease activity in these patients.</P></▼2>

Glucocorticoid-induced tumor necrosis factor receptor–related protein co-stimulation facilitates tumor regression by inducing IL-9–producing helper T cells

Kim, Il-Kyu,Kim, Byung-Seok,Koh, Choong-Hyun,Seok, Jae-Won,Park, Jun-Seok,Shin, Kwang-Soo,Bae, Eun-Ah,Lee, Ga-Eun,Jeon, Hyewon,Cho, Jaebeom,Jung, Yujin,Han, Daehee,Kwon, Byoung S,Lee, Ho-Young,Chung, Nature Publishing Group, a division of Macmillan P 2015 Nature medicine Vol.21 No.9

<P>T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (T(H)9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-kappa B-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting T(H)9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies.</P>

DBA/1JCrj Mouse에 있어서 콜라젠유도관절염에 관한 면역학적 고찰

박승규,이지연,정일엽,최용경,최인성,김효준 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.3

There is growing evidence that a variety of cytokines are secreted by cells at the inflammation sites of rheumatoid arthritis (RA) and that CDS+ B cell, a minor subtype of B cell population producing natural autoantibodies, is implicated in pathogenesis of RA. In this study, we evaluated the both cytokne levels and change of CDS+ B cell population in the peripheral blood from DBA/lJCrj mice(H-2`) which are collagen-induced arthritis(CIA) susceptible strain. Surprisingly, the healthy DBA/1JCrj and MRL/Ipr/Ipr(H-2'`) mice which were autoimmune susceptible strains tested in this experiment, showed lower IL-4, IL-6 and IL-10 levels in serum by 60% than heal-thy normal mouse strains such as Balb/c(H-2d), C57BL/6(H-2') and outbred ICR mice. MRL/lpr/ 1pr mice in which onset of spontaneous autoimmune disease is dependent upon age were similar to healthy DBA/1JCrj mice in levels of the cytokines in the serum when they are young. After the CIA(for DBA/1JCrj) or the spontaneous autoimmune disease(for MRL/lpr/Ipr) had been developed in the susceptible mouse strains, the levels of IL-6 and IL-4 in the serum were increased to 1.8- and 13-fold, respectively, as compaired with those from control groups while level of IL-10 remained relatively constant. The elevated levels of IL-4- and IL-6, however, in the serum from mice with disease status were still below those of the healthy normal mouse strains. On the other hand, CDS+ B cell population in the peripheral blood, which were reported to be increased with the development of RA for human, was rather significantly decreased for the CIA-induced DBA/lJCrj mice as evidenced by FACS analysis. It could be due to the differences in the pathogenic mechanism between CIA and RA. Taken together, our results. suggest that the levels of both these cytokines and CDS+ B cells may be utilized as important diagnostic markers for arthritides.

Free Paper Session : Upper Gastrointestinal Tract 1 ; Prevalence And Risk Factors For Atrophic Gastritis And Intestinal Metaplasia

( Na Young Kim ),( Dong Ho Lee ),( Joo Sung Kim ),( Hyun Chae Jung ),( In Sung Song ),( Kyung Phil Kang ),( Jung Hoon Lee ),( Jae Il Chung ),( Hyun Cheul Choi ),( Taek Man Nam ),( Sang Hyup Lee ),( Yo 대한소화기학회 2007 SIDDS Vol.9 No.-

Background/Aims: The prevalence of gastric cancer and Helicobacter pylori (Hp) infection is high in Korea. This study was performed to evaluate the prevalence rate of atrophic gastritis (AG) and intestinal metaplasia (IM) and their risk factors in the aspect of Hp virulence factors, environmental and host factors in normal population. Methods: The subjects consisted of 389, 135 H. pylori-negative and 254 H. pylori-positive. AG and IM were scored histologically by the Sydney classification in the antrum and body, respectively. Prevalence rate and bacterial factors such as cagA, vacA m1, m2, and oipA; environmental factors such as smoking, alcohol drinking; host factors such as genetic polymorphisms for IL-IB-511, IL-IRN, TNF-A, IL-10-592, IL-10-819, IL-10-1082, IL-8-251, IL-6-572, GSTP1, and p53 codon 72 were evaluated. Risk factors were calculated by multiple logistic regression analysis. Results: The prevalence rate of AG increased from 25%, 0% in the age of 20s, 45% and 22% in the 40s and 50% and 35% in the over 70s in the antrum and body, respectively (p<0.001). In case of IM it increased from 11.1% and 6.4% in the 30s up to 43% and 43% in over 70s in the antrum and body, respectively, (p<0.001). The positive rates of AG and IM were significantly higher in the Hp-positive than in the Hp-negative subjects. Multivariate analysis showed that the risk factors for AG were Hp infection, age ≥60, cagA and vacA m1 positive. In case of IM the risk factors were Hp infection, age ≥60, smoking, spicy food, occupation (unemployed or non professional vs. professional), IL6-572 G carrier over C/C and IL10-592 C/A vs. A/A. Conclusions: The prevalence rate of AG and IM increased proportional to age. The most risk factor for AG and IM was Hp infection. Bacterial factors were important for AG but environmental and host factors were rather important in case of IM.

Decreased Pattern-Recognition Receptor-Mediated Cytokine mRNA Expression in Obese Children With Otitis Media With Effusion

Kim, Youn Jung,Cha, Sung Ho,Lee, Ho Yun,Lee, Sun Kyu,Chung, Hee Yong,Yeo, Joon Hyung,Kim, Young Il,Yeo, Seung Geun Korean Society of Otorhinolaryngology-Head and Nec 2014 Clinical and Experimental Otorhinolaryngology Vol.7 No.1

<P><B>Objectives</B></P><P>To assess innate and humoral immune responses in middle ear effusion of obese pediatric patients with otitis media with effusion (OME).</P><P><B>Methods</B></P><P>We evaluated 219 children with OME, of whom 21 were obese and 198 were non-obese. We compared the expression in middle ear effusion of mRNAs encoding toll-like receptors (TLR) 2, 4, 5, and 9; nucleotide-binding oligomerization domains (NOD) 1 and 2; retinoic acid-inducible gene (RIG)-I; interleukins (IL)-6, -10, and -12; interferon (IFN)-γ; and tumor necrosis factor (TNF)-α mRNAs. We also compared the expression of immunoglobulins IgG, IgA, and IgM and the bacterial detection rate in the two groups.</P><P><B>Results</B></P><P>TLR2-mediated expression of IL-6 mRNA, TLR4-mediated expression of IL-6 and IL-10 mRNA, TLR5-mediated expression of IL-6, IL-10, and TNF-α mRNA, TLR9-mediated expression of IL-6 mRNA, and NOD2-mediated expression of IL-6, IL-12, and TNF-α mRNA were significantly lower in obese than in non-obese children (<I>P</I><0.05). However, concentrations of IgG, IgA, and IgM in middle ear effusion were lower in obese than in non-obese children, but none of these differences was significant (<I>P</I>>0.05).</P><P><B>Conclusion</B></P><P>Mean body mass index was higher and pattern-recognition receptor-mediated cytokine mRNA expression was lower in obese than in non-obese children with OME.</P>

A novel role for bone-derived cells in ankylosing spondylitis: Focus on IL-23

Jo, Sungsin,Koo, Bon San,Lee, Bitnara,Kwon, Eunji,Lee, Young Lim,Chung, Heekyoung,Sung, Il-Hoon,Park, Ye-Soo,Kim, Tae-Hwan Elsevier 2017 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>The main aim of this study are to explore the role of bone-derived cells (BdCs) in ankylosing spondylitis (AS) and determine the underlying molecular mechanisms of IL-23 production. Primary BdCs were isolated from diced bone of facet joints obtained during surgery from seven AS patients and seven disease control (Ct) patients. Osteoblastic activity of BdCs was assessed by measuring their alkaline phosphatase activity and by alizarin red staining. Osteoblast and endoplasmic reticulum (ER) stress-related genes were assessed by quantitative PCR, immunoblotting, immunofluorescence, and immunohistochemistry. In addition, expression of IL-23 in response to BIX (selective BIP inducer X)-induced ER stress was evaluated by qPCR and ELISA. Protein interaction and binding to IL-23 promoter were confirmed by Immunoprecipitation and Chromatin immunoprecipitation, respectively. Transcript levels of genes involved in osteoblast function, as well as of the ER stress marker were higher in the AS group than the Ct group, and elevated RUNX2, BiP and IL-23 expression were observed in the BdCs, serum, and bone biopsies from the AS group. BIX-induced ER stress stimulated osteoblastic activity and IL-23 secretion by upregulating RUNX2 expression. Furthermore, in AS BdCs, RUNX2 interacted with C/EBPβ to bind to IL-23 promoter and RUNX2 knockdown suppressed IL-23 secretion. These finding may provide a molecular mechanism involved in sustained ER stress in AS BdCs stimulates the activation of RUNX2 and C/EBPβ genes, leading to IL-23 production.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Bones and its-derived cells from patients with AS showed an increase in ER stress. </LI> <LI> IL-23 cytokine was significantly higher in AS patients than in healthy controls. </LI> <LI> Inducing ER stress in AS exhibited an increase of bone-related genes. </LI> <LI> Inducing ER stress in AS was accompanied with augmentation of IL-23 cytokine. </LI> <LI> ER stress-induced RUNX2 is involved in IL-23 secretion and bone-related genes. </LI> </UL> </P>

Silibinin polarizes Th1/Th2 immune responses through the inhibition of immunostimulatory function of dendritic cells

Lee, Jun Sik,Kim, Sang Gap,Kim, Hyung Keun,Lee, Tae-Hyung,Jeong, Young-Il,Lee, Chang-Min,Yoon, Man-Soo,Na, Yong Jin,Suh, Dong-Soo,Park, Nam Cheol,Choi, In-hak,Kim, Gi-Young,Choi, Yung Hyun,Chung, Hae Liss 2007 Journal of Cellular Physiology Vol.210 No.2

<P>Silibinin is the primary active compound in silymarin. It has been demonstrated to exert anti-carcinogenic effects and hepato-protective effects. However, the effects of silibinin on the maturation and immunostimulatory activities exhibited by dendritic cells (DCs) remain, for the most part, unknown. In this study, we have attempted to determine whether silibinin can influence surface molecule expression, dextran uptake, cytokine production, capacity to induce T-cell differentiation, and the signaling pathways underlying these phenomena in murine bone marrow-derived DCs. Silibinin was shown to significantly suppress the expression of CD80, CD86, MHC class I, and MHC class II in the DCs, and was also associated with impairments of LPS-induced IL-12 expression in the DCs. Silibinin-treated DCs proved highly efficient with regard to Ag capture via mannose receptor-mediated endocytosis. Silibinin also inhibited the LPS-induced activation of MAPKs and the nuclear translocation of the NF-κB p65 subunit. Additionally, silibinin-treated DCs evidenced an impaired induction of Th1 response, and a normal cell-mediated immune response. These findings provide new insight into the immunopharmacological functions of silibinin, especially with regard to their impact on the DCs. These findings expand our current understanding of the immunopharmacological functions of silibinin, and may prove useful in the development of therapeutic adjuvants for acute and chronic DC-associated diseases. J. Cell. Physiol. 210: 385–397, 2007. © 2006 Wiley-Liss, Inc.</P>

일 도농복합지역 저소득층 노인의 건강문제 분석 : 보건소 방문간호사업 대상자 중심으로

고일선,,이태화,이경자,이정렬,임미혜,천의영,주윤미,이계철 노인간호학회 2005 노인간호학회지 Vol.7 No.2

Purpose: The purpose of this study was to analyze the health problems of low-income aged with chronic illness living in urban-rural composite area. Method: The sample consisted of 440 aged who were receiving home care services from a public health center. MDS-HC was applied to analyze the health problems of the aged. Data were collected through a face- to-face interview by six trained interviewers from June 28 to July 15, 2004. Result: Subjects had average number of 8 health problems in both urban and rural area. Lack of preventive health care measure, pain, and visual function were the most frequent health problem. The rural aged had more pain, bowel management problems, compared to the urban aged having more urinary incontinence and indwelling catheter. There were many health problems related to falls and pressure ulcers with middle-old aged in urban, and old-old aged in rural area. Conclusion: The results of this study showed strategies for care intervention of low-income elderly to put in practice. Therefore, tailored-service for each subject should be provided.

Scoparone from Artemisia capillaris Inhibits the Release of Inflammatory Mediators in RAW 264.7 Cells upon Stimulation Cells by Interferon-γ Plus LPS

Seon Il Jang,Young-Jun Kim,Woo-Yiel Lee,Kyung Chell Kwak,Seung Hwa Baek,Gyu Beum Kwak,Young-Gab Yun,Tae-Oh Kwon,Hun Taeg Chung,Kyu-Yun Chai 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.2

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) upon stimulation by IFN-γ/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-γ/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and PGE2 in macrophages by inhibiting iNOS and COX-2 expression.