Prevalence and Risk Factors of Atrophic Gastritis and Intestinal Metaplasia in a Korean Population Without Significant Gastroduodenal Disease

Kim, Nayoung,Park, Young Soo,Cho, Sung-Il,Lee, Hye Seung,Choe, Gheeyoung,Kim, In Wook,Won, Yoo-Deok,Park, Ji Hyun,Kim, Joo Sung,Jung, Hyun Chae,Song, In Sung Wiley (Blackwell Publishing) 2008 Helicobacter Vol.13 No.4

<P>BACKGROUND AND AIM: The prevalence of gastric cancer and Helicobacter pylori infection is unacceptably high in Korea. This study was performed to evaluate the prevalence of atrophic gastritis (AG) and intestinal metaplasia (IM) and to identify their risk factors with respect to H. pylori virulence factors, and environmental and host factors, in Korean population without significant gastroduodenal disease. METHODS: The study cohort consisted of 389 subjects (> or = 16 years). AG and IM were scored histologically using the Sydney classification in the antrum and body, respectively. Prevalences and bacterial factors (i.e. cagA, vacA m1, and oipA), environmental factors (i.e. smoking and alcohol), and host factors (i.e. genetic polymorphisms of IL-1B-511, IL-1RN, TNF-A-308, IL-10-592, IL-10-819, IL-10-1082, IL-8-251, IL-6-572, GSTP1, p53 codon 72, and ALDH2) were evaluated. RESULTS: Prevalences of AG in the antrum and body were 42.5% and 20.1%, and those of IM were 28.6% and 21.2%, respectively. The presences of AG and IM were significantly higher in H. pylori-positive than in the H. pylori-negative subjects. Multivariate analysis showed that the risk factors for AG were H. pylori infection, age > or = 61 years, and cagA and vacA m1 positivity. For IM the risk factors were H. pylori infection, age > or = 61 years, a smoking history (rather than current smoking), strong spicy food, occupation (unemployed or nonprofessional vs. professional), and the presence of IL10-592 C/A as opposed to A/A. In addition, IL6-572 G carrier was found to have a protective effect against IM development as compared with C/C. CONCLUSION: H. pylori infection was most important risk factor of AG and IM. Bacterial factors were found to be important risk factor for AG but environmental and host factors were more important for IM.</P>

Association of Increased Pulmonary Interleukin-6 with the Priming Effect of Intra-Amniotic Lipopolysaccharide on Hyperoxic Lung Injury in a Rat Model of Bronchopulmonary Dysplasia

Kim, Do-Hyun,Choi, Chang Won,Kim, Ee-Kyung,Kim, Han-Suk,Kim, Beyong Il,Choi, Jung-Hwan,Lee, Myong Jin,Yang, Eun Gyeong S. Karger AG 2010 NEONATOLOGY Vol.98 No.1

<P><I>Background:</I> The authors previously demonstrated the priming effect of intra-amniotic lipopolysaccharide (LPS) on hyperoxic lung injury in a rat model of bronchopulmonary dysplasia (BPD). <I>Objectives:</I> To investigate the mechanism underlying this priming effect by determining biochemical profiles in a rat model of BPD. <I>Methods:</I> The rat model involved intra-amniotic LPS administration and postnatal hyperoxia (85%). The mRNA expressions of <I>interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), basic fibroblast growth factor (bFGF),</I> and <I>transforming growth factor </I>β<SUB><I>1</I></SUB><I> (TGF-</I>β<SUB><I>1</I></SUB><I>),</I> as well as the protein levels of IL-6, VEGF, and protein carbonyl in lung tissue were compared between the LPS plus hyperoxia, the LPS only, the hyperoxia only, and the control groups. <I>Results:</I> Morphometric analysis of lung tissues demonstrated that alveolarization was significantly inhibited only in the LPS plus hyperoxia group. IL-6 protein levels and its mRNA expression in the lungs were significantly increased only in the LPS plus hyperoxia group. Neither LPS nor hyperoxia increased IL-6 in the lungs independently. <I>bFGF</I> mRNA expression was significantly decreased in the LPS-treated groups. VEGF protein levels were significantly reduced by hyperoxia, whereas protein carbonyl levels were increased by intra-amniotic LPS or hyperoxia. No additional significant change to VEGF or protein carbonyl levels was produced by intra-amniotic LPS or hyperoxia. There were no significant differences in the mRNA expressions of <I>VEGF, VEGFR-2,</I> and <I>TGF-</I>β<SUB><I>1</I></SUB>. <I>Conclusions:</I> The priming effect of intra-amniotic LPS on hyperoxic lung injury may be associated with IL-6 elevation in the lungs.</P><P>Copyright © 2009 S. Karger AG, Basel</P>

Genetic polymorphisms of IL-23R and IL-17A and novel insights into their associations with inflammatory bowel disease.

Kim, Seung Won,Kim, Eun Soo,Moon, Chang Mo,Park, Jae Jun,Kim, Tae Il,Kim, Won Ho,Cheon, Jae Hee British Medical Association 2011 Gut: journal of the British Society of Gastroenter Vol.60 No.11

<P>To identify the associations of genetic and epigenetic variations in IL-23R and IL-17A with inflammatory bowel diseases (IBD).</P>

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>

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>

Intracellular IL-4, IL-10, and IFN-gamma levels of leukemic cells and bone marrow T cells in acute leukemia.

Park, Hun Hee,Kim, Myungshin,Lee, Bong-Hee,Lim, Jihyang,Kim, Yonggoo,Lee, Eun Jung,Min, Woo Sung,Kang, Chang Suk,Kim, Won Il,Shim, Sang In,Han, Kyungja Institute for Clinical Science] 2006 Annals of clinical and laboratory science Vol.36 No.1

<P>The quantitative levels of intracellular cytokines IL-4, IL-10, and IFN-gamma (ie, the number of bound PE-conjugated antibody molecules/cell) of leukemic cells and bone marrow T cells (bmT cells) of acute leukemia patients were analyzed by flow cytometry. One hundred, thirty-one (95 AML, 25 ALL, 11 ABL) patients were studied. The leukemic cell IL-4 level was highest in the monocytic AML group (1735 +/- 1056) and lowest in the dysplastic AML group (960 +/- 545). The IFN-gamma level was highest in the acute promyelocytic leukemia (APL) group (495 +/- 159), and lowest in the ALL group (252 +/- 119). The IL-10 level was not significantly different among the diagnosis groups. In bmT cells, the IL-10 level was highest in the dysplastic AML group (972 +/- 1049) and lowest in the APL group (397 +/- 352). The leukemic cell cytokine levels were lowest and bmT cell cytokine levels were highest in the dysplastic AML group. There were no significant correlations of these cytokine levels with 2-yr survival rate, complete remission (CR) rate, or relapse rate. The cytokine levels of bmT cells at the time of CR became normal and were not different among the diagnosis groups. In summary, leukemic cell and bmT cell cytoplasmic expression profiles of IL-4, IL-10, and IFN-gamma are characteristic for each diagnostic group of acute leukemia patients and the profiles of bmT cells are normal at the time of CR.</P>

Interaction between CD40L and CD40 Mediates Hepatic Exosomal Delivery to Kupffer Cells in Alcoholic Liver Disease

( Kyurae Kim ),( Jun-hee Lee ),( Young-ri Shim ),( Hee-hoon Kim ),( Ye Eun Kim ),( Keungmo Yang ),( Tom Ryu ),( Won-il Jeong ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Cluster of differentiation 40 (CD40) is a costimulatory molecule on antigen presenting cells including macrophages. An interesting study reported that extracellular vesicles (EVs) containing CD40L promote macrophage activation through CD40, thereby accelerating alcoholic liver diseases (ALD) in mice and patients. However, other effects of CD40L-expressing EV on Kupffer cells (KCs) have not been investigated clearly. Here, we explored CD40-mediated delivery of hepatic exosomes and its effects on KCs in acute alcoholic liver injury. Methods: To induce acute liver injury, binge ethanol drinking (4 g/kg, 40% ethanol) was performed by oral gavage into wildtype (WT) and CD40 knockout (KO) mice. Interleukin-17A (IL- 17A) positive cells were analyzed by flow cytometry. Isolated hepatocytes, KCs and DiI-stained exosomes, neutralizing antibody and dynasore were used for in vitro experiments. Results: Although the number of exosomes and mRNA expression of CD40L in hepatocytes were significantly increased by ethanol exposure, protein levels of CD40L in ethanol-induced exosomes were similar with controls, reflecting proportional increase of CD40L to the numbers of exosomes. However, freshly isolated KCs from ethanol-fed WT mice exhibited increased expression of CD40 (protein receptor of CD40L). In vitro, ethanol-induced exosomes increased CD40 expression in KCs by a TLR3-dependent manner. Moreover, DiI-stained exosomes were successfully delivered to WT KCs, but not in CD40-deficient KCs. In addition, treatments with neutralizing antibody of CD40 and dynamin inhibitor (dynasore) decreased internalization of hepatic exosomes into KCs, thereby reducing IL-1β production in KCs. Furthermore, binge ethanol drinking increased IL-17A production of γδ T cells in WT mice but not in CD40 KO mice. Conclusions: Alcohol-induced hepatic exosomes could be delivered to KCs through a CD40L/CD40-dependent endocytic uptake and they stimulate IL-1β expression in KCs, subsequently leading to IL-17A production in γδ T cells in ALD. Thus, CD40L/ CD40 axis could be a potential target to reduce IL-17A production in ALD.

흰쥐 경골의 신연 골형성술에서 염증성 싸이토카인의 발현

황일웅(Il Ung Hwang),조태준(Tae-Joon Cho),최인호(In Ho Choi),정진엽(Chin Youb Chung),유원준(Won Joon Yoo),김은희(Eun Hee Kim) 대한정형외과학회 2004 대한정형외과학회지 Vol.39 No.1

목적: 본 연구의 목적은 신연 골형성술에서의 염증성 싸이토카인의 발현 양상을 일반 골절 치유 과정과 비교하는 것이다. 대상 및 방법: 흰쥐 경골의 단순 골절 치유 모델과 신연 골형성술 모델을 대상으로 3주에 걸쳐서 단계적으로 골 조직을 채취하였다. 총 리보핵산을 추출하고 각종 염증성 싸이토카인 발현의 시간적 변화를 검사하였다. 수술 후 7일과 9일째에 조직에서 면역조직화학 검사를 통해서 IL-6의 공간적 발현 양상을 조사하였다. 결과: IL-1β, IL-6는 단순 골절 치유 과정에서 수술 후 1일째에 발현이 절정에 달하였다가 3일째부터 발현이 감소하여 수술 전 상태로 회복되었다. IL-1β는 신연 골형성술 중 신연 기간에도 발현의 변화가 없었으나 IL-6은 신연을 시작함에 따라 다시 발현이 증가하는 양상을 보였다. 면역조직화학 검사장 IL-6은 골수 세포 뿐 아니라 연골세포, 골모세포 그리고 신연 간격의 미성숙 간엽세포에서 발현이 확인되었다. 결론: 신연 변형력에 의한 IL-6의 발현이 유도되는 것을 확인하였으며, 이는 조절된 염증 반응이 신연 골형성술 과정에서 신생골 형성에 부분적으로 기여할 가능성을 시사하는 것으로 생각된다. Purpose: The purposes of this study were to investigate the expression pattern of pro-inflammatory cytokines during distraction osteogenesis and to compare these with expression during simple fracture healing. Materials and Methods: Regenerated bones from the rat tibia subjected distraction osteogenesis and simple fracture healing models were harvested over three-week periods. Temporal expressions of mRNA of pro-inflammatory cytokines were investigated by RNase protection assay. Immunohistochemical studies for IL-6 were performed in postoperative day 7 and 9 tissue section specimens. Results: IL-1β and IL-6 produced detectable signals, while IL-1α, TNF α and TNF β did not. The mRNA expressions of IL-1β and IL-6 were markedly upregulated on postoperative day 1 and then subsided to the preoperative level. IL-1β mRNA expression remained the same even when distraction began. However, IL-6 mRNA expression was reactivated during the distraction phase. Immunohistochemical study revealed the expressions of IL-6 not only at the transitional zone of the transchondroid ossification, in young osteoblasts lining newly formed trabeculae and in hematopoietic cells in the marrow but also in primitive mesenchymal cells at the distraction gap. Conclusion: Distraction strain re-induced IL-6 expression during distraction osteogenesis, which suggests that well-controlled inflammatory reaction might contribute to active new bone formation in distraction osteogenesis.

金久永의 『病因論』에 나타난 의학사상 연구

김정원(Chong Won Kim),김남일(Nam il Kim),차웅석(Wung Seok Cha) 한국의사학회 2017 한국의사학회지 Vol.30 No.1

This paper is a study on the life and clinical reasoning of Kim Goo Young (1958-2014). Offering a new perspective through his interpretation of Donguibogam (東醫寶鑑), Kim introduced his unique theory of Korean medicine, ‘The Theory of Byeongin (病因論)’. Kim recognized the confusing situation of communication between people studying Korean medicine and tried to make a new standard based on the principle that many people can share. ‘The Theory of Byeongin offers a newly constituted 󰡔Donguibogam󰡕 focusing on ‘Byeongin’ (病因, pathologic origin) which can be translated as the cause of a disease. In so doing Kim recognized ‘Byeongin as the most important factor in ‘Byeonjeung’ (辨證, classifying the origin), or the classification method of symptoms. In addition, Kim recognized how ‘Byeongin was considered to be a diseased lifestyle, and tried interpreting. The patient’s lifestyle to treat diseases. As a result, ‘The Theory of Byeongin’ is a theory consisting of an intuitive structure, reducing notable elements like Yin Yang Five Movement theory. The theory s significant characteristic is its easy application in clinical settings due the established core principles which are based on Kim’s insight and clinical experience. This study contributes to the understanding of the theoretical and clinical development of Korean medicine through deeper studies on ‘The Theory of Byeongin and Kim s medical theory.

Interleukin-1B(1L-1B) polymorphisms and gastric mucosal levels of IL-Iβ cytokine in Korean patients with gastric cancer

Chang, Young-Woon,Jang, Jae-Young,Kim, Nam-Hoon,Lee, Jae Won,Lee, Hyo Jung,Jung, Woon Won,Dong, Seok-Ho,Kim, Hyo-Jong,Kim, Byung-Ho,Lee, Joung-Il,Rin Chang KYUNG HEE UNIVERSITY MEDICAL CENTER 2006 고황의학상 수상논문집 Vol.21-22 No.-

Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1β and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1β cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR = 2.2; 95% CI = 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR = 3.4; 95% CI = 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1β levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1β production contributed to the development of intestinal-type GC in this Korean population.