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.

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>

PLZF+ Innate T Cells Support the TGF-beta-Dependent Generation of Activated/Memory-Like Regulatory T Cells

Kyeong-Cheon Jung,Byung Hyun Kang,Hyo Jin Park,Hi Jung Park,Jae-il Lee,Seong Hoe Park 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.6

PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether PLZF+ innate T cells also affect the development and function of Foxp3+ regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant PLZF+ CD4 T cells and invariant natural killer T cells, respectively, revealed that Foxp3+ T cells in these mice exhibited a CD103+ activated/memory-like phenotype. The frequency of CD103+ regulatory T cells was considerably decreased in PLZF+ cell-deficient CII-TATgPlzflu/lu and BALB/c.CD1d−/− mice as well as in an IL-4-deficient background, such as in CIITATgIL-4−/− and BALB/ c.IL-4−/− mice, indicating that the acquisition of an activated/memory-like phenotype was dependent on PLZF+ innate T cells and IL-4. Using fetal thymic organ culture, we further demonstrated that IL-4 in concert with TGF- enhanced the acquisition of the activated/memory-like phenotype of regulatory T cells. In functional aspects, the activated/memory-like phenotype of Treg cells was directly related to their suppressive function; regulatory T cells of CIITATgPIV-/- mice more efficiently suppressed ovalbumin-induced allergic airway inflammation compared with their counterparts from wild-type mice. All of these findings suggest that PLZF+ innate T cells also augmented the generation of activated/memory-like regulation via IL-4 production.

PLZF⁺ Innate T Cells Support the TGF-β-Dependent Generation of Activated/Memory-Like Regulatory T Cells

Kang, Byung Hyun,Park, Hyo Jin,Park, Hi Jung,Lee, Jae-Il,Park, Seong Hoe,Jung, Kyeong Cheon Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.6

PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether $PLZF^+$ innate T cells also affect the development and function of $Foxp3^+$ regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant $PLZF^+$ CD4 T cells and invariant natural killer T cells, respectively, revealed that $Foxp3^+$ T cells in these mice exhibited a $CD103^+$ activated/memorylike phenotype. The frequency of $CD103^+$ regulatory T cells was considerably decreased in $PLZF^+$ cell-deficient $CIITA^{Tg}Plzf^{lu/lu}$ and $BALB/c.CD1d^{-/-}$ mice as well as in an IL-4-deficient background, such as in $CIITA^{Tg}IL-4^{-/-}$ and $BALB/c.IL-4^{-/-}$ mice, indicating that the acquisition of an activated/ memory-like phenotype was dependent on $PLZF^+$ innate T cells and IL-4. Using fetal thymic organ culture, we further demonstrated that IL-4 in concert with TGF-${\beta}$ enhanced the acquisition of the activated/memory-like phenotype of regulatory T cells. In functional aspects, the activated/ memory-like phenotype of Treg cells was directly related to their suppressive function; regulatory T cells of $CIITA^{Tg}PIV^{-/-}$ mice more efficiently suppressed ovalbumin-induced allergic airway inflammation compared with their counterparts from wild-type mice. All of these findings suggest that $PLZF^+$ innate T cells also augmented the generation of activated/memory-like regulation via IL-4 production.

Glycated Serum Albumin Induces Interleukin-6 Expression in Vascular Smooth Muscle Cells

Seung-Il Baek(백승일),Byung-Yong Rhim(임병용),Koanhoi Kim(김관회) 한국생명과학회 2011 생명과학회지 Vol.21 No.1

Glycate화된 단백질이 혈관질환의 발생에 관여하는지 알아보기 위하여 glycated albumin (GA)이 혈관평활근세포에서 인터루킨-6 발현에 영향을 주는지 조사하고 또한 그 기전을 구명하였다. GA에 노출된 혈관평활근세포에서 인터루킨-6 transcript가 증가하고, 인터루킨-6 단백질의 분비가 증가하고, 또한 인터루킨-6 유전자의 promoter가 활성화되었다. GA에 의한 인터루킨-6 유전자의 promoter 활성화는 dominant negative 형태의 Toll-like receptor (TLR)-4와 myeloid differentiation factor 88 (Myd88)에 의하여 크게 감소되었지만, dominant negative 형태의 TLR-2와 TIR-domain-containing adapter-inducing interferon-β (TRIF)의 영향을 받지 않았다. 그리고 Extrcellular signal-related kinase (ERK) 억제 물질들은 GA에 의한 인터루킨-6의 분비 및 인터루킨-6 유전자 promoter 활성화를 억제하였다. 그리고 인터루킨-6 유전자의 promoter의 NF-κB-binding sequence에 변이는 GA에 의한 인터루킨-6 유전자의 promoter 활성화 억제하였다. 이러한 결과는 혈관평활근세포에서 GA에 의한 인터루킨-6 유전자 활성화에 TLR-4와 ERK 및 NF-κB가 관여함을 의미한다. Diabetes mellitus is associated with vascular complications. Diabetic patients exhibit high levels of glycated adducts in serum compared to non-diabetic individuals. The aim of this study was to investigate whether extracellular glycated albumin (GA) predisposes vascular smooth muscle cells (VSMCs) to pro-inflammatory phenotype. Exposure of rat aortic smooth muscle cells (AoSMCs) to GA not only enhanced interleukin-6 (IL-6) release but also activated promoter activity of the IL-6 gene. GA-induced IL-6 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and myeloid differentiation factor 88 (MyD88), but not by dominant-negative-forms of TLR-2 and TIR-domain-containing adapter-inducing interferon-β (TRIF). Extracellular signal-regulated kinase (ERK) inhibition and diphenyleneiodium (DPI) also attenuated IL-6 induction by GA. Mutation at the nuclear factor-κB (NF- κB)-binding site in the IL-6 promoter region suppressed promoter activation in response to GA. The present study proposes that GA would contribute to inflammatory reaction in the stressed vasculature by inducing IL-6 in VSMCs, and that TLR-4, EKR, and NF-κB play active roles in the process.

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>

Different shapes of Al₂O₃ particles induce differential cytotoxicity via a mechanism involving lysosomal destabilization and reactive oxygen species generation

Kim, Byung Il,Joo, Yong Hoon,Pak, Pyo June,Kim, Joong-Su,Chung, Namhyun 한국응용생명화학회 2015 Applied Biological Chemistry (Appl Biol Chem) Vol.58 No.3

The biological effects of nano- and micro-sized $Al_2O_3$ particles are hypothesized to differ according to the shapes as well as the sizes of the particles. Thus, the mechanisms of interleukin (IL)-$1{\beta}$ production and the association between the shape of the $Al_2O_3$ particle and its cytotoxicity in macrophage-like THP-1 cells were investigated using particles with three different shapes [$N-Al_2O_3$ (<30 nm), $S-Al_2O_3$ ($2-4nm{\times}100-800nm$), $L-Al_2O_3$ ($2-4nm{\times}2800nm$)]. Levels of IL-$1{\beta}$ production and cytotoxicity were concentration-dependent and were in the following order: $S-Al_2O_3$ > $N-Al_2O_3$ > $L-Al_2O_3$. Stimulus of THP-1 cells by $Al_2O_3$ particles led to lysosomal destabilization, generation of intracellular reactive oxygen species (ROS), and subsequent release of cathepsin B. The magnitude of the stimulus was dependent on the shapes and aspect ratios of the particles. Additional results suggested that caspase-1 (NALP3 inflammasome) activation and IL-$1{\beta}$ production followed cathepsin B release. In addition, the cell death induced by $Al_2O_3$ particles was closely related with cathepsin B leakage. The mode of cell death was necrotic as much as apoptotic. We conclude that $Al_2O_3$ particles induce different levels of IL-$1{\beta}$ production and cytotoxicity depending on their particle shapes or aspect ratios. The current finding may support the development of safe forms of $Al_2O_3$ particles.

간장 ( 肝腸 ) 및 담도 ( 膽道 ) : B형 활동성 간염 환자에서 단기 Prednisolone과 ARA - AMP 겸용 치료의 경과에 따른 면역 지표의 변화에 관한 연구

민영일(Young Il Min),장린(Rin Chang),김병호(Byung Ho Kim),장영운(Young Woon Chang),이정일(Joung Il Lee),황이숙(Yi Sook Hwang),김정원(Jeong Won Kim),김효종(Hyo Jong Kim) 대한소화기학회 1990 대한소화기학회지 Vol.22 No.3

N/A Withdrawal of corticosteroids in patients with chronic type B hepatitis is frequently associated with enhanced cellular immune response to hepatitis B virus. This immunolgic rebound generally results in a transient reduction in levels of HBV-DNA and DNA polymerase, and seldom results in clearance of HBeAg. There was a pilot study that the combination of a short course of prednisone followed by ARA-AMP was potentially synergistic. The object of this study was to determine the effect of short term prednisolone followed by ARA-AMP on the immune system in patients with chronic active ltepatitis-B. Patients were started 40 mg of prednisolone daily for 4 weeks. After prednisolone therapy was discontinued, patients received no medication for 2 weeks. ARA-AMP was then given for 4 weeks at a dose of 500 mg daily. Immune parameters such as T cell subsets, IL, production, NK cell activeity, and LAK cell activity were tested before and during treatement period. The resullts were as follows. 1) Basal IL2 production in CAH-B (71.3 unit/ml) was lower than that of normal control (p<0.025). Basal NK activity, T4/T8 ratio and LAK activity of CAH-B were similar to those of normal control. 2) After prednisolone treatment, IL2 production, NK cell activity and LAK cell activity were significantly lower than those of basal value. 3) After induction of immune rebound, IL, production increased to 84.8 unit/ml (basal 71.3 unit/ml,

방풍의 항염 효과 기전

노성일 ( Sung Il Noh ),김상돈 ( Sang Don Kim ),박성철 ( Sung Cheul Park ),서병윤 ( Byung Yun Seo ),염승룡 ( Seung Ryong Yeom ),권영달 ( Young Dal Kwon ),신병철 ( Byung Cheul Shin ),송용선 ( Yung Sun Song ) 한방재활의학과학회 2005 한방재활의학과학회지 Vol.15 No.2

목적 : 방풍은 임상적으로 관절염을 포함한 다양한 염증성 질환 치료제로 사용되어 왔다. 본 연구에서는 인간 비만세포를 이용하여 세포 독성에 영향을 주지 않는 농도에서 방풍의 항염 효과 및 그 기전을 검토했다. 방법 : 인간의 HMC-1세포를 IMDM에서 페니실린, 스트렙토마이신, 모노티오글리세린를 첨가하여 배양하고 방풍추출액을 투여하였다. 그 다음 MTT, ELISA, RT-PCR, 세포내 칼슘측정, 핵단백분석을 이용하여 TNF-α, IL-6, IL-8 각각의 형성과 mRNA발현, 세포내 칼슘 수준, NF-κB 발현에 대한 방풍추출액의 반응을 측정하고 통계처리 하였다. 결과 : 방풍은 PMA와 calcium ionophore A23187로 활성화된 비만세포에서 세포내 칼슘 수준과 NF-κB, TNF-α와 IL-6의 발현을 억제 시켰고 RT-PCR을 이용한 mRNA 발현에서 TNF-α와 IL-6의 발현을 억제하였다. 결론 : 방풍은 비만세포내 칼슘 수준 및 NF-κB의 활성을 억제하고 염증성 세포 활성 물질인 TNF-α와 IL-6의 분비도 억제하여 항염 효과를 나타냄을 암시하고 있다.

麻醉前處置劑 Flunt (Ro 5-4200)과 Meperidine HCI의 比較的 硏究

金庸樂,咸秉文,崔重立,郭一龍 한국의 현대의학사 1974 한국의 현대의학 Vol.7 No.1