인간 재조합 인터루긴-32 면역조절작용에 대한 유세포 분석

이광수,김영관,채정일,심정현,김은미,강형식,김수현,윤도영,명평근 충남대학교 생물공학연구소 2006 생물공학연구지 Vol.12 No.-

Xenotransplantation of porcine organs has the potential to overcome the severe shortage of human tissues and organ available for human transplantation. however, it remains various hurdles for clinical xenotransplantation. In pig and mouse xenotransplantation, porcine xenograft evoke a strong cellular rejection response in immunocompetent host and grafts are destroyed within a week. This cellular immune response could involved both T cells and NK cells. A number of groups have shown that human NK cells can recognize and damage porcine endothelial cells. In addition, human T cells can respond to porcine endothelial cells through both direct and indirect mechanisms. Cellular rejection of porcine tissues requires T cells, particularly CD4^(+) cells. A new cytokine recombinant human interleukin-32α,β(IL-32α,β) has a role innate and acquired immune system. In order to investigate the role of recombinant mouse IL-18 and recombinant human IL-32α,β in xenograft rejection, we transplanted the PK(15) cells to C57BL/6 mice with or without intraperitoneal injection of recombinant mouse IL-18 or recombinant human IL-32 α,β. It was analyzed the population of NK cell, T cell and B cell in the C57BL/6 mice transplanted with PK(15) cells and recombinant mouse IL-18 or recombinant human IL-32α,β by flow cytometry analysis. As a result, lymph node and thymus of PK15/IL18, PK15/IL32α and PK15/IL32β injected group were increased to T cell activation population than normal injected groups. CD8^(+) T cells were decreased in lymph node of PK15/IL18, PK15/IL32α and PK15/IL32β injected groups. CD4^(+) T cells were increased in lymph node cell of PK15/IL32α and PK15/IL32β injected group and also, B cell population were increased in lymph node cell and spleen of PK15/IL18, PK15/IL32α and PK15/IL32β injected group. Therefore, we suggest that recombinant mouse IL-18 and recombinant human IL-32α,β suppress xenograft rejection in cellular xenotransplantation.

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>

정신분열병과 22번 염색체 인터루킨-2 수용체 β-chain 유전자의 연관성

김용구,이민수,김 인,곽동일,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.3

연구배경 : 정신분열병이 유전적이라고 제시하는 많은 역학 연구와 유전자 연구에도 불구하고, 이 질환의 유전방식과 질병유전자는 밝혀져 있지 않다. 본 연구에서는 정신분열병과 22번 염색체 장완의 11.2-12부위에 위치한 Interleukin-2수용체 β chain 유전자간에 유전적 연합을 조사하고자 정신분열병 환자 93명과 정상대조군 97명 대상으로 중합효소연쇄반응을 이용하여 Interleukin-2 수용체 β chain (IL-2Rβ) 유전자의 다형성 분포를 조사하였다. 연구방법 : 환자군은 DSM-Ⅲ-R 진단기준에 따라 임상아형(망상형, 붕괴형, 미붕괴형, 잔류형)으로 분류하였다. 음성 및 양성 정신분열병으로 분류하기위해 Positive and Negative Syndrome Scale(PANSS)을 사용하였다. Genomic DNA를 전혈 임파구에서 추출한 후, IL-2Rβ 유전자좌를 분석하기 위해 dinucleotide(GT)n 염기배열순서를 중합효소연쇄반응을 이용하여 증폭시켰다. 연구결과 : IL-1Rβ의 대립유전자는 모두 8가지 종류이고, guanine-thymine의 반복된 149 염기쌍을 시작으로 151, 153, 155, 157, 159, 161, 163 염기쌍의 형태를 보였다. 정신분열병 환자군과 정상대조군간에 도형접합체 및 이형접합체 빈도의 유의한 차이는 없었다. 환자군과 정상대조군의 대립유전자 분포의 빈도는 통계적으로 유의한 차이가 없었다. 더욱이 각각의 대립유전자 분포에서도 양군간 유의한 차이는 없었다. 또한 동질의 아형으로 분류해 보기위해 임상아형, 양성 및 음성증상군, 가족력의 유무에 따라 비교적 동질적인 표현형을 가진 집단으로 나눈 후 대립유전자 분포를 비교해 보았으나 통계적으로 유의한 차이를 보이지 않았다. 결 론 : 본 연구에서는 Interleukin-2 수용체 β chain 유전자가 정신분열병의 병인론에 관련된다는 가설을 지지할 만한 긍정적 소견을 얻지 못했다. Background : While a significant genetic predisposition to schizophrenia has been proposed, the mode of inheritance or nature of etiological factors is unknown. Previous reports of a genome-wide survey for schizophrenia susceptibility genes have indicated a possible region of linkage on chromosome 22. In order to test the possibility that the interleukin-2 receptor β chain(IL-2Rβ) gene on chromosome 22 is of etiological importance in schizophrenia, a case-control association study was conducted. Methods : Subjects were ninety-three schizophrenic patients with a diagnosis of schizophrenia by DSM-Ⅲ-R criteria and ninety-seven normal controls, Schizophrenic patients were divided by clinical phenotypes such as DSM-Ⅲ-R diagnostic subtypes, positive and negative symptoms, and family history so as to increase the homogeneity of schizophrenics. Genomic DNA was extracted from whole blood lymphocytes according to standard procedures. The DNA was used to study a dinucleotide repeat in the IL-2Rβ gene. To reveal the dinucleotide polymorphism. genomic DNA of subjects was amplified by polymerase chain reactions(PCR). Results : At the IL-2Rβ gene locus, all the previously reported alleles(eight different alleles) of a dinucleotide polymorphism were identified. There was no significant difference between number of heterozygosity in schizophrenic patients and in normal controls. There was no significant difference in the distribution of frequencies of alleles between schizophrenics and normal controls. In addition, there was no significant difference in the allele frequencies among subtypes of schizophrenic patients according to DSM-Ⅲ-R diagnostic subtypes, positive and negative symptoms, and family history. Conclusion : The present study did not detect a difference in frequencies of alleles of a dinucleotide polymorphism at the IL-2Rβ gene locus between schizophrenic patients and normal controls. These results do not supports an evidence that IL-2Rβ gene plays, a major role in the etiology of schizophrenia.

제대혈 유래 인간 비만세포에서의 세포증식 및 히스타민 분비에 대한 Interleukin 9의 영향

안강모 ( Kang Mo Ahn ),이광신 ( Kwang Shin Lee ),신미용 ( Mi Yong Shin ),박화영 ( Hwa Young Park ),안연화 ( Yeon Hwa Ahn ),손대열 ( Dae Yeul Son ),이상일 ( Sang Il Lee ) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2002 소아알레르기 및 호흡기학회지 Vol.12 No.4

목적: Interleukin 9(IL-9)는 Th2 싸이토카인의 일종으로서 알레르기 염증반응의 병태생리에 관여하는 것으로 알려져 있다. 본 연구에서는 IL-9이 주요 알레르기 염증세포의 하나인 인간 비만세포에 어떠한 영향을 주는지를 알아보기 위하여 시행되었다. 방법:본 연구에서는 인간 제대혈에서 CD34 (+) 세포를 분리한 후 stem cell factor(SCF), IL-3, IL-6를 투여함으로써 비만세포를 선택적으로 배양하였다. 8주간 배양이 끝 Purpose:Interleukin-9(IL-9), one of Th2-type cytokines, might be important in the pathophysiology of allergic diseases. We investigated the effect of IL-9 on human mast cells by assessing cell proliferation and histamine release. Methods: Human umbilical

코디세핀이 마우스 복강 대식세포에서 전염증성 사이토카인의 생성에 미치는 영향

서민정(Min-Jeong Seo),강병원(Byoung-Won Kang),김민정(Min-Jeong Kim),이혜현(Hye-Hyeon Lee),서권일(Kwon-il Seo),김광혁(Kwang-Hyuk Kim),정영기(Yong-Kee Jeong) 한국식품과학회 2014 한국식품과학회지 Vol.46 No.1

본 연구는 동충하초(Cordyces militaris) 유래의 기능성 물질인 코디세핀의 면역활성을 검증하기 위하여 C57BL6 마우스 복강 대식세포를 이용하여 코디세핀이 대식세포의 활성화에 미치는 영향에 대하여 시험하였다. 그 결과 LPS에 의해 유도된 마우스 복강세포는 코디세핀의 작용에 의해 IL-1β, IL-12, TNF-α의 염증성 사이토카인의 생성이 증대되어 초기 염증매개 반응을 유도하여 선천면역반응의 활성화와 그리고 면역작용에 있어 후기 적응면역의 전환으로의 T 림프구의 활성화가 예상된다. 또한 IL-6의 생성증대로 활성화된 T 림프구에 의해 B 림프구의 항체생성반응을 매개하는 면역반응도 상승할 것으로 사료된다. 그리고 대식세포에 의한 염증반응에서 염증매개인자인 NO와 H₂O₂의 생성을 증대시킴에 따라 대식세포의 독성작용을 활성화시켜 염증반응을 효과적으로 유도할 것으로 보이며, 또한 H₂O₂의 후기 생성을 저해하였는데 이는 염증반응에 유도될 수 있는 세포의 손상으로부터 세포를 보호할 수 있을 것으로 사료된다. 따라서 코디세핀은 외부인자로부터 염증매개성 면역반응의 증강작용을 나타내는 것으로 사료된다. The effect of cordycepin purified from Cordyceps militaris on macrophage activation was investigated in peritoneal macrophages isolated from C57BL6 mice. Lipopolysaccharide-induced mouse peritoneal cells showed that cordycepin treatment increased the expression of the inflammatory cytokines interleukin (IL)-1β, IL-12, and tumor necrosis factor-α (TNF-α), leading to early inflammation-mediated reactions, the activation of immunological responses, and T lymphocyte activation. T lymphocytes, activated by a greater production of IL-6, resulted in antibody-generating immune reactions, suggesting that cordycepin was effective at inducing immunological responses. Consistent with the increase in the inflammation-mediating factors including nitric oxide (NO) and hydrogen peroxide (H₂O₂), the toxic response of macrophages was activated and effectively induced inflammation. These findings demonstrate that cordycepin is involved in reducing cell injury provoked by inflammatory reactions. Therefore, these results suggest that cordycepin treatment of mouse peritoneal cells induces inflammation-mediated immunological responses and immunostimulation.

The α-adrenoceptor mediation of the immunomodulatory effects of electroacupuncture in DNP-KLH immunized mice

Lee, Youngseop,Kim, Sun Kwang,Kim, Yangseok,Lee, Hyejung,Shin, Min-Kyu,Hong, Moo-Chang,Min, Byung-Il,Bae, Hyunsu WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2007 東西醫學硏究所 論文集 Vol.2007 No.-

Our previous study demonstrated that successive electroacupuncture (EA) at ST36 acupoint reduces IgE production in BALB/c mice immunizec with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH) by suppression of the Th2 cell lineage development. Here, we report that pretreatment of phentolamine (α-adrenoceptor antagonist, 10 mg/kg, i.p.) completely blocks the EA-induced suppression of antigen-specifie and total IgE levels in serum and IL-4 production in anti-CD3 mAb-activated splenocytes in DNP-KLH immunized mice. The results suggest that α-adrenoceptor play an important role in mediating the suppressive effects of EA on IgE production and Th2 cell response in DNP-KLH immunized mice.

Characterization of IL-3, IL-5, GM-CSF - induced Eosinophils from Human CD34+ Cord Blood Cells

( Kwang Shin Lee ),( Kang Mo Ahn ),( Seung Yeon Nam ),( Dae Yeul Son ),( Se Chang Han ),( Man Yong Han ),( Sang Il Lee ) 대한 소아알레르기 호흡기학회(구 대한소아알레르기 및 호흡기학회) 1999 소아알레르기 및 호흡기학회지 Vol.9 No.4

Characterization of age‐associated exhausted CD 8 ⁺ T cells defined by increased expression of Tim‐3 and PD ‐1

Lee, Kyoo‐,A,Shin, Kwang‐,Soo,Kim, Ga‐,Young,Song, You Chan,Bae, Eun‐,Ah,Kim, Il‐,Kyu,Koh, Choong‐,Hyun,Kang, Chang‐,Yuil John Wiley and Sons Inc. 2016 Aging Cell Vol.15 No.2

<P><B>Summary</B></P><P>Aging is accompanied by altered T‐cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 (PD‐1), in the T cells of aged mice emphasize the importance of investigations into the relationship between T‐cell exhaustion and aging‐associated immune dysfunction. In this study, we demonstrate that T‐cell immunoglobulin mucin domain‐3 (Tim‐3), another exhaustion marker, is up‐regulated on aged T cells, especially CD8<SUP>+</SUP> T cells. Tim‐3‐expressing cells also produced PD‐1, but Tim‐3<SUP>+</SUP>PD‐1<SUP>+</SUP>CD8<SUP>+</SUP> T cells had a distinct phenotype that included the expression of CD44 and CD62L, from Tim‐3<SUP>−</SUP>PD‐1<SUP>+</SUP> cells. Tim‐3<SUP>+</SUP>PD‐1<SUP>+</SUP>CD8<SUP>+</SUP> T cells showed more evident properties associated with exhaustion than Tim‐3<SUP>−</SUP>PD‐1<SUP>+</SUP>CD8<SUP>+</SUP> T cells: an exhaustion‐related marker expression profile, proliferative defects following homeostatic or TCR stimulation, and altered production of cytokines. Interestingly, these cells produced a high level of IL‐10 and induced normal CD8<SUP>+</SUP> T cells to produce IL‐10, which might contribute to immune dysregulation in aged mice. The generation of Tim‐3‐expressing CD8<SUP>+</SUP> T cells in aged mice seems to be mediated by encounters with antigens but not by specific infection, based on their high expression of CD49d and their unbiased TCR Vβ usage. In conclusion, we found that a CD8<SUP>+</SUP> T‐cell population with age‐associated exhaustion was distinguishable by its expression of Tim‐3. These results provide clues for understanding the alterations that occur in T‐cell populations with age and for improving dysfunctions related to the aging of the immune system.</P>

Effect of Feed Selenium-lysine Supplementation on Milk Compositions and Serum Biochemical Indices in Saanen Dairy Goats

Tae-Il Kim,Dong-Hyun Lim,Tai-Young Hur,Seung-Min Ha,Hyun-Jong Kim,Seong-Min Park,Ji-Hoo Park,Sang-Bum Kim,Ji-Hwan Lee,Hyun-Joo Lim,Jeong-Sung Jung,Ha-Yeon Jeong,Jay Lee,Kwang-Seok Ki,Vijayakumar Mayak 경상대학교 농업생명과학연구원 2019 농업생명과학연구 Vol.53 No.4

An experiment was carried out to assess the effect of feed selenium-lysine (Se-Lys) supplementation on milk compositions and serum biochemical indices in Saanen dairy goats in Korea. A total of twelve 36 months old Saanen lactating dairy goats (47±6.21 kg) fed the similar dry matter intake twice a day at 2% of BW (DMI) (10.9% moisture of concentrate and 19% moisture of roughage), milk yield (2.5 kg/d) and parity (2) were randomly selected and subjected for the present study, divided into two groups with six goats in each group. The goats in the control group received rice hulls (10 g/ day) only, and did not receive Se-Lys; goats in the treatment group were fed 0.06 g of Se-Lys with 10 g of rice hulls every day before feeding roughage for six weeks. The milk sample was collected every week, and its compositions were analyzed. The results of the present study showed that there is no significantly increased milk production in Se-Lys treated group goats when compared with control group goats. But, Se-Lys treatment significantly increased the milk protein content (3.98±0.16%), fat (3.72±0.27%), lactose (4.07±0.14%), total solids (12.51±0.28%) and urea (14.42±1.45 mg/dl) content as compared to the control group goats (p<0.05). The somatic cell counts (207,740±28.81 cells/ml) were significantly lower in the Se-Lys treated group than in the control group (p<0.05). Also, the results of the current study showed that supplementation of Se-Lys were significantly decreased the blood biochemical indices of IL-6 (34.34±6.04 pg/ml), TNT-α (0.56±0.22 ng/ml), MDA (5.07±1.03 ng/ml), GPx-1 (9.07±5.17 ng/ml), sCD4 (2.64±1.02 ng/ml) and sCD8 (5.08±2.08 ng/ml) level when compared with without addition of Se-Lys group dairy goats (p<0.05). On the other hand, the selenoprotein P (1,580.18±127.62 ng/ml) level was significantly higher in Se-Lys supplemented group than in the control group (p<0.05). Based on the study results, it was concluded that feed Se-Lys supplementation may improve milk yield with positively improved protein, fat, lactose, total solids, urea content, and biochemical indices without negative effects on milk production traits.

Regulation of Proinflammatory Mediators via NF- <i><i>κ</i></i> B and p38 MAPK-Dependent Mechanisms in RAW 264.7 Macrophages by Polyphenol Components Isolated from Korea <i>Lonicera japonica THUNB</i>

Park, Kwang-Il,Kang, Sang-Rim,Park, Hyeon-Soo,Lee, Do Hoon,Nagappan, Arulkumar,Kim, Jin A,Shin, Sung Chul,Kim, Eun Hee,Lee, Won Sup,Chung, Hyon-Jong,An, Su Jin,Kim, Gon Sup Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-

<P><I>Lonicera japonica THUNB.</I>, which abundantly contains polyphenols, has been used as a traditional medicine for thousands of years in East Asian countries because of the anti-inflammation properties. This study aimed to investigate the anti-inflammatory mechanism of polyphenol components isolated from Korea <I>L. japonica T.</I> by nuclear factor-kappaB (NF-<I><I>κ</I></I>B) and mitogen-activated protein kinases (MAPKs) pathway. Polyphenols significantly decreased lipopolysaccharide- (LPS-) induced mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as mRNA expression of tumor necrosis factor-alpha, interleukin- (IL-) 1<I><I>β</I></I>, and IL-6. Moreover, polyphenols inhibited nuclear translocation of NF-<I><I>κ</I></I>B p65, phosphorylation/degradation of the inhibitor of <I><I>κ</I></I>B, and phosphorylation of p38 MAPK, whereas the extracellular signal-regulated kinase and Janus N-terminal kinase were not affected. These results indicate that polyphenol components isolated from Korea <I>L. japonica T.</I> should have anti-inflammatory effect on LPS-stimulated RAW 264.7 cells through the decrease of proinflammatory mediators expression by suppressing NF-<I><I>κ</I></I>B and p38 MAPK activity.</P>