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)

IL-17A induces osteoblast differentiation by activating JAK2/STAT3 in ankylosing spondylitis

Jo, Sungsin,Wang, Sung Eun,Lee, Young Lim,Kang, Suman,Lee, Bitnara,Han, Jinil,Sung, Il-Hoon,Park, Ye-Soo,Bae, Sang-Cheol,Kim, Tae-Hwan BioMed Central 2018 Arthritis research & therapy Vol.20 No.-

<P><B>Background</B></P><P>IL-17A has recently emerged as a potential target that regulates the extensive inflammation and abnormal bone formation observed in ankylosing spondylitis (AS). Blocking IL-17A is expected to inhibit bony ankylosis. Here, we investigated the effects of anti IL-17A agents in AS.</P><P><B>Methods</B></P><P>TNFα, IL-17A, and IL-12/23 p40 levels in serum and synovial fluid from patients with ankylosing spondylitis (AS), rheumatoid arthritis (RA), osteoarthritis (OA), or healthy controls (HC) were measured by ELISA. Bone tissue samples were obtained at surgery from the facet joints of ten patients with AS and ten control (Ct) patients with noninflammatory spinal disease. The functional relevance of IL-17A, biological blockades, Janus kinase 2 (JAK2), and non-receptor tyrosine kinase was assessed in vitro with primary bone-derived cells (BdCs) and serum from patients with AS.</P><P><B>Results</B></P><P>Basal levels of IL-17A and IL-12/23 p40 in body fluids were elevated in patients with AS. JAK2 was also highly expressed in bone tissue and primary BdCs from patients with AS. Furthermore, addition of exogenous IL-17A to primary Ct-BdCs promoted the osteogenic stimulus-induced increase in ALP activity and mineralization. Intriguingly, blocking IL-17A with serum from patients with AS attenuated ALP activity and mineralization in both Ct and AS-BdCs by inhibiting JAK2 phosphorylation and downregulating osteoblast-involved genes. Moreover, JAK2 inhibitors effectively reduced JAK2-driven ALP activity and JAK2-mediated events.</P><P><B>Conclusions</B></P><P>Our findings indicate that IL-17A regulates osteoblast activity and differentiation via JAK2/STAT3 signaling. They shed light on AS pathogenesis and suggest new rational therapies for clinical AS ankylosis.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (10.1186/s13075-018-1582-3) contains supplementary material, which is available to authorized users.</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>

(무기환)戊己丸의 RAW 264.7 세포에 대한 항염증작용 연구

김일현 ( Il Hyun Kim ),최종환 ( Chong Hwan Choi ),이세원 ( Se Won Lee ),송용선 ( Yung Sun Song ) 한방재활의학과학회 2013 한방재활의학과학회지 Vol.23 No.3

ObjectivesThe aim of this study was to investigate anti-inflammatory activity of Mugi-hwan (MGH) Water Extract. MethodsCells were treated with 2 ug/ml of LPS 1 hour prior to the addition of MGH. Cell viability was measured by MTS assay. The production of NO was determined by reacting cultured medium with Griess reagent. The expression of COX-2, iNOS and MAPKs was investigated by Western blot, RT-PCR. The content of level of cytokines (PGE2, IL-6, in media from LPS-stimulated Raw 264.7 cells was analyed by ELISA kit. ResultsMGH inhibited the production of NO, PGE2, IL-6 as well as the expressions of iNOS, COX-2 in the murine macrophage, RAW 264.7 cells. MGH also had suppression effects of LPS induced MAPKs activation. ConclusionsThese results suggest that MGH has an anti-inflammatory therapeutic potential, which may result from inhibition of MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes. (J Korean Med Rehab 2013;23(3):27-35) ObjectivesThe aim of this study was to investigate anti-inflammatory activity of Mugi-hwan (MGH) Water Extract. MethodsCells were treated with 2 ug/ml of LPS 1 hour prior to the addition of MGH. Cell viability was measured by MTS assay. The production of NO was determined by reacting cultured medium with Griess reagent. The expression of COX-2, iNOS and MAPKs was investigated by Western blot, RT-PCR. The content of level of cytokines (PGE2, IL-6, in media from LPS-stimulated Raw 264.7 cells was analyed by ELISA kit. ResultsMGH inhibited the production of NO, PGE2, IL-6 as well as the expressions of iNOS, COX-2 in the murine macrophage, RAW 264.7 cells. MGH also had suppression effects of LPS induced MAPKs activation. ConclusionsThese results suggest that MGH has an anti-inflammatory therapeutic potential, which may result from inhibition of MAPK phosphorylation, thereby decreasing the expression of pro-inflammatory genes. (J Korean Med Rehab 2013;23(3):27-35)

A Study of Korean-American Writers(11): Chang-rae Lee`s The Surrendered

( Il Hwan Lee ) 국민대학교 어문학연구소 2014 語文學論叢 Vol.33 No.-

삼황사심탕(三黃瀉心湯)이 난황 알부민으로 유도된 알레르기 Mouse모델에서 항알레르기 효과

최종환 ( Chong Hwan Choi ),금선오 ( Seo Oh Keum ),이세원 ( Se Won Lee ),김일현 ( Il Hyun Kim ),이하일 ( Ha Il Lee ),송용선 ( Yung Sun Song ) 한방재활의학과학회 2014 한방재활의학과학회지 Vol.24 No.3

Objectives In this study, we investigated the inhibitory effects of Samhwangsasim-tang (S.H) on the allergic response caused by ovalbumin(OVA) sensitization and challenge in BALB/c mice. Methods The experimental animals were divided into five groups; 1) normal as negative control, 2) OVA-sensitized mice, 3) OVA-sensitized mice treated with 200 mg/kg of S.H 200, 4) OVA-sensitized mice treated with 400 mg/kg of S.H 400, and 5) OVA-sensitized mice treated with 5 mg/kg of Dexamethasone (Dex). Antigen sensitization for allergic mouse model was performed with twice injection of OVA for 2 weeks. After secondary injection, S.H was administrated orally into mice every day for 13 days and the inhibitory effect of S.H on allergic responses was evaluated. Results Treatment of S.H into allergic mice reduced significantly ear edema and infiltration of immune cells in ear tissues induced with OVA challenge in a dose-dependent manner. S.H reduced significantly the serum levels of Total Immunoglobulin(Ig)G and IgE, and particularly inhibited the production of OVA-specific IgE, but not OVA-specific IgG. The serum level of proinflammatory cytokine TNF-α and Th2-associated cytokine IL-4 also were significantly decreased by S.H adminstration in a dose denpendent manner. S.H attenuated OVA-induced secretion of IFN-γ, but not IL-12 which is a cytokine inducing the development of Th1 cells. It also reduced significantly the secretion of IL-4, which is a cytokine inducing the development of Th2 cells, after splenocytes were stimulated with OVA. However the secretion of IL-5 and IL-13 was influenced weakly or a little. Conclusions These results indicate that S.H could reduce the allergic response through inhibition of antigen-specific IgE and Th2-inducing cytokines. It suggest that S.H may be available clinically for the treatment of allergic patients. (J Korean Med Rehab 2014;24(3): 71-85)

Tumor Necrosis Factor-α-Activated Human Adipose Tissue–Derived Mesenchymal Stem Cells Accelerate Cutaneous Wound Healing through Paracrine Mechanisms

Heo, Soon Chul,Jeon, Eun Su,Lee, Il Hwan,Kim, Hoon Soo,Kim, Moon Bum,Kim, Jae Ho The Society for Investigative Dermatology, Inc 2011 The Journal of investigative dermatology Vol.131 No.7

Human adipose tissue–derived mesenchymal stem cells (ASCs) stimulate regeneration of injured tissues by secretion of various cytokines and chemokines. Wound healing is mediated by multiple steps including inflammation, epithelialization, neoangiogenesis, and proliferation. To explore the paracrine functions of ASCs on regeneration of injured tissues, cells were treated with tumor necrosis factor-α (TNF-α), a key inflammatory cytokine, and the effects of TNF-α-conditioned medium (CM) on tissue regeneration were determined using a rat excisional wound model. We demonstrated that TNF-α CM accelerated wound closure, angiogenesis, proliferation, and infiltration of immune cells into the cutaneous wound in vivo. To assess the role of proinflammatory cytokines IL-6 and IL-8, which are included in TNF-α CM, IL-6 and IL-8 were depleted from TNF-α CM using immunoprecipitation. Depletion of IL-6 or IL-8 largely attenuated TNF-α CM-stimulated wound closure, angiogenesis, proliferation, and infiltration of immune cells. These results suggest that TNF-α-activated ASCs accelerate cutaneous wound healing through paracrine mechanisms involving IL-6 and IL-8.

<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>

Lactic Acid Bacteria Improves Peyer`s Patch Cell-Mediated Immunoglobulin A and Tight-Junction Expression in a Destructed Gut Microbial Environment

( Sung Hwan Kim ),( Woonhee Jeung ),( Il Dong Choi ),( Ji Woong Jeong ),( Dong Eun Lee ),( Chul Sung Huh ),( Geun Bae Kim ),( Seong Soo Hong ),( Jae Jung Shim ),( Jung Lyoul Lee ),( Jae Hun Sim ),( Yo 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.6

To evaluate the effects of lactic acid bacteria (LAB) on Peyer`s patch cells, mice were treated with a high dose of kanamycin to disturb the gut microbial environment. The overarching goal was to explore the potential of LAB for use as a dietary probiotic that buffers the negative consequences of antibiotic treatment. In vitro, LAB stimulated the production of immunoglobulin A (IgA) from isolated Peyer`s patch cells. Inflammation-related genes (TNF-α, IL-1β, and IL-8) were up-regulated in Caco-2 cells stimulated with lipopolysaccharide (LPS), while tight-junction-related genes (ZO-1 and occludin) were down-regulated; the effects of LPS on inflammatory gene and tight-junction gene expression were reversed by treatment with LAB. Mice treated with a high dose of kanamycin showed increased serum IgE levels and decreases in serum IgA and fecal IgA levels; the number of Peyer`s patch cells decreased with kanamycin treatment. However, subsequent LAB treatment was effective in reducing the serum IgE level and recovering the serum IgA and fecal IgA levels, as well as the number of Peyer`s patch cells. In addition, ZO-1 and occludin mRNA levels were up-regulated in the ileum tissues of mice receiving LAB treatment. Lactic acid bacteria can enhance the intestinal immune system by improving the integrity of the intestinal barrier and increasing the production of IgA in Peyer`s patches. Lactic acid bacteria should be considered a potential probiotic candidate for improving intestinal immunity, particularly in mitigating the negative consequences of antibiotic use.

생쥐의 B 세포에서 anti-CD40과 rIL-4로 유도된 싸이토카인 생산에 대한 자오가의 효과

성일창 ( Il Chang Sung ),김형환 ( Hyung Hwan Kim ),안덕균 ( Duk Kyun Ahn ),이용섭 ( Yong Sup Lee ),서영배 ( Young Bae Seo ),최호영 ( Ho Young Choi ) 대한본초학회 2003 大韓本草學會誌 Vol.18 No.2

N/A Objectives : In order to study the anti-allegy effect of water extract of Acanthopanacis senticosi Radix (ASR) on the B-cells from healthy Balblc mice. Methods : The cytotoxicity of ASR was measured with the murine normal lung fibroblast cells by modified SRB assay. And the murine splenic B-cells was stimulated with anti-CD40 mAb and rIL4. The various cytokines related with allergy were measured by flow-cytometry and by RT-PCR with electophoresis. Results : The anti-allegy effects to ASR were identified and observed. The cytotoxicity of ASR on mouse lung fibroblast cells showed no significant activities. ASR had inhibitory effect on CD23+, CD69+, and IgE expression by ASR with anti-CD40 mAb plus rL-4-stimulated murine splenic B-cells. ASR had inhibitory effect on cytokines (E-lb, IL-4, IL-6, IL-10, TNF-a, TGF-81, INF-Y) and transcript expression and IgE production by ASR with anti-CD40 mAb plus rIL-4-stimulated murine splenic B-cells. Conclusion : We concluded that ASR showed anti-allegy effect on murine splenic B-cells.