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.

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.

Gene therapy of intracranial glioma using interleukin 12-secreting human umbilical cord blood-derived mesenchymal stem cells.

Ryu, Chung Heon,Park, Sang-Hoon,Park, Soon A,Kim, Seong Muk,Lim, Jung Yeon,Jeong, Chang Hyun,Yoon, Wan-Soo,Oh, Won-il,Sung, Young Chul,Jeun, Sin-Soo Mary Ann Liebert 2011 Human gene therapy Vol.22 No.6

<P>Clinical trials of gene therapy using a viral delivery system for glioma have been limited. Recently, gene therapy using stem cells as the vehicles for delivery of therapeutic agents has emerged as a new treatment strategy for malignant brain tumors. In this study, we used human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) as delivery vehicles with glioma-targeting capabilities, and modified interleukin-12 (IL-12p40N220Q; IL-12M) as a novel therapeutic gene. We also engineered UCB-MSCs to secret IL-12M (UCB-MSC-IL12M) via tetrameric cell-permeable peptide (4HP4)-mediated adenoviral transduction. We confirmed the migratory capacity of UCB-MSC-IL12M toward GL26 mouse glioma cells by an in vitro migration assay and in vivo injection of UCB-MSC-IL12M into the ipsilateral hemisphere of implanted gliomas in C57BL/6 mice. In vivo efficacy experiments showed that intratumoral injection of UCB-MSC-IL12M significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with control mice. Antitumor effects were associated with increased local IL-12M levels, followed by interferon-γ secretion and T-cell infiltration in intracranial gliomas, as well as antiangiogenesis. Interestingly, tumor-free mice after UCB-MSC-IL12M treatment were resistant to ipsilateral and contralateral tumor rechallenge, which was closely associated with tumor-specific long-term T-cell immunity. Thus, our results provide the rationale for designing novel experimental protocols to induce long-term antitumor immunity against intracranial gliomas using UCB-MSCs as an effective delivery vehicle for therapeutic cytokines including IL-12M.</P>

人蔘이 羊水感染에 의한 早産에 미치는 영향

尹成獻,趙亨來,金瞳一,李泰均,南景琇 대한한의학회 부인과학회 2000 大韓韓方婦人科學會誌 Vol.13 No.2

This study was performed to investigate the effect of Panax ginseng on preterm labor by amniotic infection. The results of this study were as follows; 1. Interleukin-6(IL-6) production induced lipopolysaccharide(LPS) or Interleukin-1β (IL-19) was inhibited by Panax ginseng hot water-extracts. 2. Production of tumor necrosis factor-α (TNT-α) was not inhibited by Panax ginseng on L929 cytotoxicity assay. 3. Phospholipase A_2(PLA_2) induced LPS in WISH cell was inhibited by Panax ginseng, and also induced IL-1β was inhibited low concentration. 4. PGE_2 production induced LPS and IL-1β was inhibited by Panax ginseng hot water-extracts on PGE_2 enzyme immunoassay. 5. Leukotriene C4 (LTC4) production induced LPS and also IL-1β was inhibited by Panax ginseng hot water-extracts. 6. Panax ginseng may be useful for treatment of preterm labor by amniotic infection because it can inhibit inflammation response induced infection.

Involvement of E-selectin in recruitment of endothelial progenitor cells and angiogenesis in ischemic muscle

Oh, Il-Young,Yoon, Chang-Hwan,Hur, Jin,Kim, Ji-Hyun,Kim, Tae-Youn,Lee, Choon-Soo,Park, Kyung-Woo,Chae, In-Ho,Oh, Byung-Hee,Park, Young-Bae,Kim, Hyo-Soo American Society of Hematology 2007 Blood Vol.110 No.12

<B>Abstract</B><P>E-selectin plays critical roles in tethering leukocytes to endothelial cells (ECs). We studied the role of E-selectin in endothelial progenitor cell (EPC) homing and vasculogenesis. After ischemia, the expression of E-selectin on ECs peaked 6 to 12 hours and returned to baseline at 24 hours, whereas the level of soluble E-selectin (sE-selectin) in serum increased over 24 hours and remained high at day 7. Mouse bone marrow-derived EPCs expressed not only E-selectin but also its ligand. Homing of circulating EPCs to ischemic limb was significantly impaired in E-selectin knock-out mice, as well as wild-type mice pretreated with blocking antibody against E-selectin, which was rescued by local sE-selectin injection. Mechanism for this is that sE-selectin stimulated not only ECs to express ICAM-1, but also EPCs to secrete interleukin-8 (IL-8), leading to enhanced migration and incorporation to ECs capillary formation. In therapeutic aspect, local treatment with sE-selectin enhanced efficacy of EPC transplantation for vasculogenesis and salvage of ischemic limb. Conversely, when E-selectin was knocked down by E-selectin small interfering RNA, blood flow recovery after EPC transplantation was significantly impaired. But this impaired vasculogenesis was rescued by sE-selectin. In conclusion, these data demonstrate E-selectin is a pivotal molecule for EPCs' homing to ischemic limb and vasculogenesis.</P>

Graphene–Ionic Liquid Based Hybrid Nanomaterials as Novel Lubricant for Low Friction and Wear

Khare, Varsha,Pham, Minh-Quan,Kumari, Nitee,Yoon, Hae-Sung,Kim, Chung-Soo,Park, Jae-IL,Ahn, Sung-Hoon American Chemical Society 2013 ACS APPLIED MATERIALS & INTERFACES Vol.5 No.10

<P>Hybrid nanomaterials offer potential scope for an increasing number of novel applications when engineered to deliver usefully functional properties. Recent advancements in the design of new material products that result from interactions among different compositions at the nanoscale and microscale has led to innovative ways to fabricate and process hybrids with altered structural physicochemical properties. An example is the development of novel “lubricants” that make use of ionic liquids (ILs) and their ability to induce exploitable molecular assemblies at the IL–graphene interface. In the present study, we report the potential of graphene–IL hybrid nanomaterials for engineering applications with a focus on “lubricant” properties to reduce frictional forces to enhance tribological performance. The present contribution outlines the wear and tribological properties (friction and lubrication) of a highly viscous IL [BMIM][I] and its comparison with its nanohybrid material counterpart. Detailed structural–microstructural investigations of the nanohybrid materials were performed using X-ray diffraction and microscopic techniques employing scanning electron (SEM), transmission electron (TEM), and high resolution transmission electron (HRTEM) microscopies. A comparative study of the morphology of friction track and wear behavior was assessed by SEM and TEM. These characteristic properties within and outside the friction track were further correlated with physical and chemical interactions obtained by contact angle measurements and Raman spectroscopy and energy dispersive analysis by X-ray (EDAX).</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2013/aamick.2013.5.issue-10/am302761c/production/images/medium/am-2012-02761c_0016.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am302761c'>ACS Electronic Supporting Info</A></P>

골수이식 후 사이토카인과 골교체 생화학적표지자의 변화 및 상관관계

민우성,강무일,한제호,강성구,오기원,이원영,김혜수,문성대,손현식,신완식,김춘추,윤건호,차봉연,이광우,손호영 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.1

Background : Loss of bone mass is usually detected after BMT. The causes of bone loss are related with gonadal dysfunction and immunosuppressants. Cytokines, especially IL-6, play an important role in the pathogenesis of postmenopausal osteoporosis. However, the pathogenetic role of cytokines in post-BMT bone loss is unknown and data on the changes of cytokines in accordance with bone turnover markers are scarce. The aim of this study is to assess the relationship of bone turnover markers and cytokines of peripheral blood and bone marrow before and after allogeneic BMT. Methods : This prospective study included two analyses. The first was a study of 46 BMT recipients, examining the relationship between bone turnover markers and cytokines of serum which were measured before and 1, 2, 3, 4 week and 3 months after BMT. The second was a study of 14 BMT patients, measuring bone marrow plasma cytokines such as IL-6 and TNF-? at post-BMT 3 week and bone turnover marker at the same time to assess the relationship beween two parameters. Results : Serum ICTP, bone resorption marker, increased progressively until 4 weeks (peak) after BMT and then decreased thereafter. Serum osteocalcin, bone formation marker, decreased progressively until 3 weeks after BMT and then increased thereafter. There was positive correlation between serum ICTP and bone marrow IL-6 levels at the post-BMT 3 week with a statistical significance, but the correlation between bone turnover markers and bone marrow TNF-? or peripheral blood cytokines was not found. Conclusion : Our data suggest that the progressive increase of bone resorption after BMT is related with the increase of bone marrow IL-6, which is a potent stimulator of bone resorption in vivo(J Kor Soc Endocrinol 15:85-96, 2000).

Cadmium Sulfate가 肝組織에 미치는 影響에 관한 形態學的 硏究

윤강호,박경란,김수일,노승무,김원식 충남대학교 의과대학 지역사회의학연구소 1991 충남의대잡지 Vol.18 No.2

Cadmium is well known toxic heavy metal which has been related with various pathologic conditions of liver, kindney, testis, cardiovascular system and central nervous system etc.. In this experiment, cadmium sulfate (1.2mg/100gm b.w.) was given intravenously into the mouse (Balb - C, b. w. 20 - 25gm) via tail vein for the study on morphological changes of liver. On the 8hours, 16hours and 24hours after administration, mice were sacrificed under ether anesthesia, liver was removed, then, a part of liver was fixed in 10% neutral buffered formalin solution, processed routinely, stained with hematoxylin & eosin, and observed under light microscope. Otherwise, the remainder portion of liver tissue was prefixed in 1.5% glutaraldehyde solution, postfixed in the 1% osmium tetraoxide solution, embedded with Epon 840, and observed under transmission electron microscope(H-7000, Hitachi Co.). The results obtained were as followings ; 1. On light microscopic observation, hemorrhagic necrosis at the zone Ⅰ and zone Ⅱ with congestion of hepatic lobules were found. 2. On transmission electron microscopic observation, cisternal dilation of RER & SER, autophagic vacuoles, myelin figures, and certain electron dense materials within the hepatocytes were found. Although this observations were limited in mice, the above findings of its acute effects on liver morphology will serve morphological basis for the better understanding of toxic effects on liver after chronic exposure or multiple interactions with other toxic substances.

요골동맥을 이용한 관동맥 조영술의 유용성

윤정한,이승환,이한요,김장영,김일회,최윤종,이형준,이명옥,김승년,황성오,홍인수,최경훈 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.10

위암환자에서 BrdU에 의하여 유도되는 Fragile sites의 발현

윤숙자,한승로,정옥,김수일,박경란,이영호,김원식 충남대학교 의과대학 지역사회의학연구소 2001 충남의대잡지 Vol.28 No.1

The expression frequency of BrdU-induced fragile sites was examined in stomach cancer patients to determine whether this parameter could be used as a marker of genetic susceptibility in at-risk individuals. G banding performed to detect fragile sites. No difference was found in expression frequency between the stomach cancer patients and a group of normal individuals(p=0.7). This indicates that the expression frequency of BrdU-induced fragile sites is not a suitable marker for assessing genetic susceptibility in stomach cancer patient.