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      • Analysis of IFNG-regulated genes in the uterine endometrium during early pregnancy in pigs

        Inkyu Yoo,Yohan Choi,Heewon Seo,Jisoo Han,Minjeong Kim,Hakhyun Ka 한국발생생물학회 2013 한국발생생물학회 학술발표대회 Vol.2013 No.8

        The implantation process in pigs is initiated when the conceptus begins secretion of estrogen, the signal for maternal recognition of pregnancy, and cytokines including interleukin-1β(IL1B), interferon delta (IFND) and interferon gamma (IFNG). Our previous study showed that IFNG receptors, IFNGR1 and IFNGR2, were expressed in the uterine endometrium during the estrous cycle and early pregnancy. However, the molecular and cellular mechanism of IFNG in the uterine endometrium in pigs is poorly understood. To determine the role of IFNG on the uterine endometrium during the implantation period, we took advantage of RNA-Seq analysis using explant tissues treated with IFNG in the presence of estrogen and progesterone, and found that many genes including CXCL9, CXCL10, CXCL11, IDO1, IL15, IL15RA, TNFSF10 (TRAIL), and WARS were up-regulated by IFNG. Additional analysis in the uterine endometrial tissues from day (D) 12 and D15 of the estrous cycle and from D12, D15, D30, D60, D90 and D114 of pregnancy determined the expression of these IFNG-regulated genes in pigs by quantitative real-time PCR Results showed that expression of CXCL9, CXCL10, and IDO1 dramatically increased on D15 of pregnancy, and expression of CXCL11 and TNFSF10 was high during mid- to term pregnancy. These results indicate that IFNG regulates immune-associated genes in the uterine endometrium in a stage-specific fashion during pregnancy, and may play a critical role to support the establishment and maintenance of pregnancy at the fetomaternal interface in pigs.

      • Association of <i>Interferon Gamma</i> Polymorphism with Ossification of the Posterior Longitudinal Ligament in the Korean Population

        Kim, Ki Tack,Kim, Dong Hwan,Chung, Jun-Young,Lee, Soojeong,Joo, Jaesoon,Nah, Seong-Su,Song, Ho-Yeon,Kim, Hak-Jae Informa Healthcare 2012 Immunological investigations Vol.41 No.8

        <P>In this study, we investigated whether genetic polymorphisms of the interferon gamma (<I>IFNG)</I> gene were associated with the susceptibility of ossification of the posterior longitudinal ligament (OPLL) in the Korean population. To observe the association between the <I>IFNG</I> gene and the susceptibility of OPLL, we genotyped 135 OPLL patients and 222 control subjects for a single nucleotide polymorphism (SNP, rs2430561) and a microsatellite (CA<SUB>n</SUB> repeats, rs3138557) located in the first intron of the <I>IFNG</I> gene, using the direct sequencing and gene scan method. The numbers of microsatellites (CA<SUB>13</SUB> and CA<SUB>15</SUB>) were significantly changed in the OPLL patients. A combined analysis of the genotype of rs2430561 and the number of microsatellites revealed that the OPLL was associated with frequencies of CA<SUB>13</SUB>-AA, CA<SUB>15</SUB>-AA and CA<SUB>15</SUB>-AT. Our results suggest that the <I>IFNG</I> gene may be one of the factors determining the OPLL in the Korean population. However, larger collaborative and biological studies are needed to confirm these results.</P>

      • Class II Trans Activator and Major Histocompatibility Complex Class II Molecules: Expression at the Maternal-Conceptus Interface in Pigs

        Inkyu Yoo,Jisoo Han,Soogil Chae,Soohyung Lee,Hakhyun Ka 한국동물생명공학회(구 한국동물번식학회) 2017 발생공학 국제심포지엄 및 학술대회 Vol.2017 No.10

        For the successful pregnancy maternal immune response must be regulated to tolerate the semi-allogenic conceptus. In adaptive immunity, major histocompatibility complex class II (MHC class Ⅱ) molecules play critical role in presenting foreign antigens to the other immune cells. During early pregnancy in pigs, various types of endometrial cells, including epithelial cells, vascular endothelial cells, stromal cells, and infiltrated immune cells are activated by conceptus-derived interferon gamma (IFNG) and express immune regulatory molecules. Therefore, we determined the expression and regulation of MHC class II molecules, swine leukocyte antigen (SLA) -DM, -DO, -DR and -DQ and their transcription coactivator CIITA at the maternal-conceptus interface. We obtained endometrial tissue samples from day (D) 12 and D15 of the estrous cycle and D12, D15, D30, D60, D90 and D114 of pregnancy. Quantitative real-time PCR anaysis showed that mRNA levels of all genes dramatically increased on D15 of pregnancy. To determine the effect of interferon-gamma (IFNG) on SLAs and CIITA expression, we took advantage of explant culture and found that all of SLAs and CIITA were up-regulated by IFNG in a dose-dependent manner. Immunohistochemistry showed that CIITA protein was localized to vascular endothelial cells and stroma near the luminal epithelium on D15 of pregnancy. SLA-DQ protein is localized to stromal leukocytes and vascular endothelial cells during the estrous cycle and early pregnancy with the highest signal intensity on D15 of pregnancy. These results indicate that CIITA and MHC class II molecules are expressed in the uterine endometrium in a cell-type and stage-specific fashion during pregnancy, and may play a critical role in regulation of maternal immune response to support the establishment and maintenance of pregnancy at the maternal- conceptus interface in pigs.

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        Enhanced Rg3 negatively regulates Th1 cell responses

        Minkyoung Cho,최가람,심인보,Yeonseok Chung 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.1

        Background: Korean Red Ginseng (KRG; Panax ginseng Meyer) is a widely used medicinal herb known to exert various immune modulatory functions. KRG and one of its purified components, ginsenoside Rg3, are known to possess anti-inflammatory activities. How they impact helper T cell-mediated responses is not fully explored. In this study, we attempted to evaluate the effect of KRG extract (KRGE) and ginsenoside Rg3 on Th1 cell responses. Methods: Using well-characterized T cell in vitro differentiation systems, we examined the effects of KRGE or enhanced Rg3 on the Th1-inducing cytokine production from dendritic cells (DC) and the naïve CD4þ T cells differentiation to Th1 cells. Furthermore, we examined the change of Th1 cell population in the intestine after treatment of enhanced Rg3. The influence of KRGE or enhanced Rg3 on Th1 cell differentiation was evaluated by fluorescence-activated cell sorting, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction. Results: KRGE significantly inhibited the production level of IL-12 from DCs and subsequent Th1 cell differentiation. Similarly, enhanced Rg3 significantly suppressed the expression of interferon gamma (IFNg) and T-bet in T cells under Th1-skewing condition. Consistent with these effects in vitro, oral administration of enhanced Rg3 suppressed the frequency of Th1 cells in the Peyer’s patch and lamina propria cells in vivo. Conclusion: Enhanced Rg3 negatively regulates the differentiation of Th1 cell in vitro and Th1 cell responses in the gut in vivo, providing fundamental basis for the use of this agent to treat Th1-related diseases.

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