Up-Regulation of Interleukin-4 Receptor Expression by Interleukin-4 and CD40 Ligation via Tyrosine Kinase-Dependent Pathway

Kim, Hyun-Il,So, Eui-Young,Yoon, Suk-Ran,Han, Mi-Young,Lee, Choong-Eun Korean Society for Biochemistry and Molecular Biol 1998 Journal of biochemistry and molecular biology Vol.31 No.1

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4 (IL-4) and CD40 ligation in B cell activation, we have examined the effect of CE40 cross-linking on the IL-4 receptor expression in human B cells using anti-CE40 antibody. We observed that IL-4 and anti-CD40 both induce IL-4 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in a significant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4 action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

Up - Regulation of Interleukin - 4 Receptor Expression by Interleukin - 4 and CD40 Ligation via Tyrosine Kinase - Dependent Pathway

( Hyun Il Kim,Eui Young So,Suk Ran Yoon,Mi Young Han,Choong Eun Lee ) 생화학분자생물학회 1998 BMB Reports Vol.31 No.1

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4(IL-4) and CD40 ligation in B cell activation we have examined the effect of CD40 cross-linking on the IL-40 receptor expression in human B cells using anti-CD40 antibody. We observed that IL-4 and anti-CD40 both induce IL-40 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in asignificant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

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>

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>

퇴행성 관절염에서 Interleukin-6와 Soluble Interleukin-6 Receptor

장재석 ( Jae Suk Chang ),정용갑 ( Yong Gab Jeong ),조우신 ( Woo Shin Cho ),빈성일 ( Seong Il Bin ),엄규황 ( Kyu Hwang Ym ),김정화 ( Jung Hwa Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.3

Objective: Unlike other soluble receptors, the soluble interleukin-6 receptor (sIL-6R) cooperates with IL-6 to activate gp130 of effector cell. As the IL-6 and sIL-6R are important in the rheumatoid disease, this study was designed to measure concentration of IL-6 and sIL-6R in synovium and synovial fluid of the degenerative arthritis. Methods: The synovium and synovial fluid were obtained during total knee replacement arthroplasty. The synovium was taken from eleven patients, and synovial fluid taken from sixteen patients. Same patients between two groups were seven. Tissue cultures of the synovial tissues were done with 10% FBS for 72 hours. After irrigation, thery were incubated for 48 hours without FBS, and the culture media and the synovial fluid were collected after centrifuged at 2500rpm for 10 minutes. The level of IL-6 and sIL-6R were measured by quantitative sandwich enzyme immunoassay technique. Results: In the synovium, the IL-6 level was 5.1±0.12ng/ml, and the sIL-6R level was 0.41±0.25ng/ml. In the synovial fluid, the IL-6 level was 0.09± 0.15ng/ml, and the sIL-6R level was 10.37±3.28ng/ml. These results show that IL-6 concentration was measured highly in two groups, especially in synovium (sixty times), and the sIL-6R concentration was measured significantly high in synovial fluid (twenty-five times). Conclusion: The IL-6 and sIL-6R were elevated in degenerative arthrits. We confirmed the source of IL-6 was synovium (very high in synovial tissue culture media), but we need further study for the source of sIL-6R as it was remarkably elevated as IL-6 and its level was lower than serum.

복막 중피 세포에서 IL-1β 자극에 의한 MCP-1과 RANTES의 생성

송인숙,이상구,박정식,양원석,김순배,윤견일 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.5

Human peritoneal mesothelial cells may have a great potential to secrete chemokines, growth factors, adhesion molecules, and various cytokines stimulated with proinflammatory cytokines during peritoneal infection. In the course of peritonitis, rapid neutrophil cell influx and subsequent monocytic cell influx can be observed. It has been demonstrated that human peritoneal mesothelial cells secrete a C-X-C chemokine, IL-8, which contributes to the recruitment of neutrophil influx during peritoneal infection. However, the production and role of C-C chemokines have not been fully defined in human peritoneal mesothelial cells. This study was performed to evaluate the production of MCP-1 and RANTES and their influence on the chemotaxis of monocytes when human peritoneal mesothelial cells were stimulated with IL-1β. Mesothelial cells obtained by enzymatic digestion of pieces of human omentum and stimulated with a various doses and times of IL-1β. The expression of MCP-1 and RANTES mRNA was measured by Northern bloassay and the expression of their proteins was analyzed by ELISA. To evaluate their function, monocytes chemotaxis assay was performed using a 48-well chemotactic chamber. Cultured human peritoneal mesothelial cells appeared to be polygonal at confluence using phase contrast microscope. Indirect immunofluorescent staining demonstrated that the mesothelial cells reacted positively with anti-cytokeratin antibody and anti-vimentin antibody. The expression of MCP-1 and RANTES mRNA increased in response to IL-1β in time and dose dependent manner. The protein levels of MCP-1 and RANTES with stimulation of 1.0ng/mL of IL-1β for 24 hours were higher than those without(30.0±2.22 vs 3.55±0.74ng/105cells and 1.53±0.41 vs 0.11±0.02ng/105cells respectively, p$lt;0.05, n=6). Chemotaxis assay showed that the supernatants from human peritoneal mesothelial cells with stimulation of IL-1β for 24 hours had significantly higher chemotaxis of monocytes than those without(71±3.4% vs 50±2.9%, p$lt;0.05, n=6). Coincubation of sup with stimulation and antibodies to MCP-1 or RANTES(20μL/mL, lOμL/mL, respectively) resulted in a significant inhibition of chemotaxis of monocytes by 33% and 12%(47±3.1% and 62±3.0% respectively, p$lt;0.05, n=6). Human peritoneal mesothelial cells are capable of the expression of MCP-1 and RANTES mRNA and the production of their proteins in response to IL-1β. Functionally, mesothelial cells derived Mand RANTES may contribute to the recruitment of monocytes and amplify the inflammatory process. Thus, human peritoneal mesothelial cells play an important role during peritoneal infection.

Up-Regulation of Interleukin-4 Receptor Expression by Interleukin-4 and CD40 Ligation via Tyrosine Kinase-Dependent Pathway

Lee, Choong-Eun,Kim, Hyun-Il,So, Eui-Young,Yoon, Suk-Ran,Han, Mi-Young The Korea Science and Technology Center 1998 BMB Reports Vol.31 No.1

Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4(IL-4) and CD40 ligation in B cell activation we have examined the effect of CD40 cross-linking on the IL-40 receptor expression in human B cells using anti-CD40 antibody. We observed that IL-4 and anti-CD40 both induce IL-40 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in asignificant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

담배 니코틴에 의한 사람 태아 성상세포에서 종양괴사인자(TNF-α)의 발현 억제작용

손일홍,이성익,양현덕,한선정,석승한,이재규,김재현,박주영,문형인,이성수,Son, Il-Hong,Lee, Sung-Ik,Yang, Hyun-Duk,Han, Sun-Jung,Suk, Seung-Han,Lee, Jai-Kyoo,Kim, Jae-Hyun,Park, Joo-Young,Moon, Hyung-In,Lee, Sung-Soo 대한화학회 2007 대한화학회지 Vol.51 No.3

니코틴은 사람 대식세포에서 interleukin 2 (IL-2)와 종양괴사인자 (tumor necrosis factor-alpha; TNF-α) 가 생성되는 것을 억제하는데, 이러한 억제작용은 cytokine 유전자 발현 중 전사단계에서 전사인자의 활성을 억제함으로써 일어난다. 이러한 니코틴의 면역반응 억제작용은 아프타성궤양 및 궤양성대장염, 알레르기성폐 포염, 건초열 등에서도 보고되고 있다. 만일 중추신경계에서도 위와 같은 니코틴의 면역억제 작용이 일어난 다면 다발성경화증과 같은 면역반응 매개질환의 치료에 새로운 전기가 마련될 수 있을 것이다. 본 연구에서 는 중추신경계의 여러 면역반응 매개질환의 병태생리에 대한 이해를 넓히고자, 이미 알려진 니코틴의 cytokine 생성억제가 사람 중추신경계의 성상세포에서도 일어남을 확인하고 그 억제기전을 밝히고자 하였다. 이를 위 하여 사람 태아 성상세포에 다양한 농도의 니코틴과 IL-1β를 처리한 다음 TNF-α mRNA의 발현 정도와 NF- κB의 활성을 비교, 분석하여 다음과 같은 결과를 얻었다. 1. 사람 태아 성상세포를 0.1-20 μg/ml의 니코틴으로 처리해 본 결과 10 μg/ml 이상의 농도에서 세포독성능이 나타나기 시작하였다. 2. 사람 태아 성상세포에 IL- 1β를 처리하면 2시간만에 TNF-α mRNA가 최대로 발현되었으며 그 이후로는 점진적으로 감소하였다. 3. 사 람 태아 성상세포를 1 및 0.1 μg/ml의 니코틴으로 전처리한 후 IL-1β로 자극한 군에서는 IL-1β 단독 처리군에 비해 TNF-α mRNA의 발현이 감소하는 양상을 보였다. 1 μg/ml의 니코틴을 처리한 경우에는 8시간 이후부터 TNF-α mRNA의 발현이 현저하게 감소하여 12시간에 최대로 감소하였다. 또한 0.1 μg/ml의 니코틴을 처리한 군에서는 24시간에 가장 현저하게 감소하였다. 4. 성상세포에 IL-1β로 처리한 군에서는 강력한 NF-κB의 활성 을 확인할 수 있었으며, 니코틴을 전처리하고 IL-1β 자극한 군에서는 NF-B의 활성이 감소하였다. 결론적으로 일정농도 이상의 니코틴은 세포독성효과를 나타내나 적정한 농도와 시간 경과후 니코틴은 사람 태아 성상세포에서 IL-1β에 의해 유도되는 TNF-α의 발현 감소를 유도하며, 이는 NF-κB의 활성을 감소시킴으로써 나타난다고 생각된다. The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

FPD 스토커 유틸리티 설계에 관한 연구

김석동,김광겸,김동일,김우성 호서대학교 반도체제조장비국산화연구센터 2000 반도체 장비기술 논문집 Vol.2000 No.-

본연구에서는 FPD 스토커 유틸리티 데이타 베이스부분과 이와 관련한 Registry system을 집중적으로 분석하여 FPD 스토커 유틸리티 설계에 관한 여구를 수행하였다. GUI를 통해 윈도우 환경에서 구성하기 위해 MFC(Microsoft Foundation Class)의 멀티플(Mutiple) 다큐멘트(Document)/뷰(View), 즉 MDI 구조를 사용하였다. 어플리케이션에서 사용되는 데이터를 관리하는 다큐멘트와 다큐멘트의 내용을 사용자에게 보여주는 역할과 사용자로부터 발생된 이벤트를 처리하는 부분으로 구성하였다. GUI가 실행되어 메인 쓰레드(Main Thread)가 만들어 지면 모든 데이터베이스 조작들과 모든 다큐멘트/뷰 상호작용을 처리되며다음과 같이 수행하였다. 1) 데스크탑(Desktop)매니저 생성 2) 메시지 버스를 담당하는 메시지 버스 쓰레드를 생성 3) 레지스트리(Registry)의 데이터를 이용하여 설정 4) 데이터베이스 초기화 스토커(Stocker) 그래픽 사용자 인터페이스(GUI)는 기계 조작자가 쉽고 편하게 Material의 저장과 검색을 할 수 있도록 엔진(Engine)르 가지고 통신하는 어플리케이션을 개발하였다.

Adiponectin is a negative regulator of NK cell cytotoxicity.

Kim, Kun-Yong,Kim, Jae Kwang,Han, Seung Hyun,Lim, Jong-Seok,Kim, Keun Il,Cho, Dae Ho,Lee, Myeong-Sok,Lee, Jeong-Hyung,Yoon, Do-Young,Yoon, Suk Ran,Chung, Jin Woong,Choi, Inpyo,Kim, Eunjoon,Yang, Young American Association of Immunologists 2006 Journal of Immunology Vol.176 No.10

<P>NK cells are a key component of innate immune systems, and their activity is regulated by cytokines and hormones. Adiponectin, which is secreted from white adipose tissues, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. In this study the effect of adiponectin on NK cell activity was investigated. Adiponectin was found to suppress the IL-2-enhanced cytotoxic activity of NK cells without affecting basal NK cell cytotoxicity and to inhibit IL-2-induced NF-kappaB activation via activation of the AMP-activated protein kinase, indicating that it suppresses IL-2-enhanced NK cell cytotoxicity through the AMP-activated protein kinase-mediated inhibition of NF-kappaB activation. IFN-gamma enhances NK cell cytotoxicity by causing an increase in the levels of expression of TRAIL and Fas ligand. The production of IFN-gamma, one of the NF-kappaB target genes in NK cells, was also found to be suppressed by adiponectin, accompanied by the subsequent down-regulation of IFN-gamma-inducible TRAIL and Fas ligand expression. These results clearly demonstrate that adiponectin is a potent negative regulator of IL-2-induced NK cell activation and thus may act as an in vivo regulator of anti-inflammatory functions.</P>