• 대한치과교정학회지
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• 제23권2호
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• pp.229-248
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• 1993

결합 조직의 대사를 억제하고, 골조직이나 골세포의 골기질 대사 역시 억제하는 것으로 알려져 있는 $Interferon-\gamma(IFN-\gamma)$의 교정치료에의 이용 가능성을 평가하기 위하여, 교정력에 의한 골 개조 과정에서 중심적 역할을 하는 것으로 알려진 치주인대 세포를 primary culture하여 배양된 세포에 $IFN-\gamma$를 투여함으로써 이것이 골조직 기질의 합성능에 미치는 영향에 대하여 관찰하였다. $IFN-\gamma$는 세포의 DNA합성능을 약하게 증가시켰으며, 세포내 DNA 총량에는 영향을 미치지 않았다. 따라서 이 실험에서 사용한 용량의 $IFN-\gamma$는 세포에 독성이 없다고 할 수 있으며, 다른 결합조직 세포에서 나타나는 항증식 효과와는 반대되는 결과였다. $IFN-\gamma$는 비교원성 단백질(NCP)의 합성을 증가시키는 양상을 나타내었으나, 교원질(CDP)의 합성은 감소시키는 경향을 보여, 총단백질에 대한 교원질의 합성비율은 $IFN-\gamma$에 의해 용량 의존적으로 감소하였다. 또한 교원질의 mRNA양은 단백질 합성과 유관하게 $IFN-\gamma$에 의해 억제되었다. 따라서 $IFN-\gamma$는 교원질 합성의 전사과정 혹은 그 이후의 과정에 영향을 미칠 것으로 예상할 수 있다. 한편 Indomethacin의 투여로 $IFN-\gamma$에 의해 억제된 교원질의 합성이 영향을 받지 않았기 때문에 $IFN-\gamma$에 의한 교원질 합성 과정에 prostaglandin이 관련되지 않았음을 알 수 있었다. 반면 fibronectin의 합성은 10 및 100 U/ml의 $IFN-\gamma$ 투여시에는 영향을 받지 않았으나, 1000U/ml의 $IFN-\gamma$투여시에는 유의한 증가를 나타내어, 교원질에서와는 다른 영향을 나타내었다. 또한 mRNA steady state level에서도 $IFN-\gamma$는 교원질의에서와는 달리 fibronectin mRNA 양에는 영향을 미치지 않았다. 즉 $IFN-\gamma$ fibronectin 유전자 발현에 영향을 미치는 부위는 전사나, 전사후 변형단계가 아닌 단백질 합성단계에서 영향을 미침을 보여주었다. 따라서 $IFN-\gamma$ 교원질과 fibronectin합성 조절 영향을 미치는 부위 서로 다름을 알 수 있겠다. Alkaline phospatase의 활성은 10-1000 U/ml의 $IFN-\gamma$를 투여시 약하게 증가시키는 경향을 보였으나 석회화가 일어날 정도로 높게 증가시키지는 못했다. 따라서 $IFN-\gamma$는 골기질의 주성분인 type I 교원질의 합성을 선택적으로 억제하는 기능과 alkaline phosphatase의 활성을 크게 증가시키지 못한 점 등으로 미루어 볼 때, 골개조를 억제하는 방향으로 작용한다고 볼 수 있으며, 교정치료 과정중 골개조를 억제하는 부위에서 사용을 시도해 볼 수 있겠다.

• 한국어병학회지
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• 제16권3호
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• pp.139-146
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• 2003

We have investigated the biological effects of recombinant IL-1$\beta$ (rIL-1$\beta$) on the expression of antiviral genes such as Myxovirus-3 (MX-3) and Interferon regulating factor-1 (IRF-1), which are related to type I interferon. When ten micrograms of rIL-1$\beta$ were treated, we observed the stimulatory effect on the expression of these antiviral genes. Interestingly, at the early stage of stimulation, these genes were down-regulated and then up-regulated by the results obtained that the expressions of these genes were decreased at day 1 post-injection and gradually increased at day 3 post-injection. Thus, the stimulatory effect of rIL-1$\beta$ on the expression of MX-3 and IRF-3 gene might be an indirect stimulatory effect because significant up-regulation was delayed until day 3 post-injection.

• Journal of Microbiology and Biotechnology
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• 제29권11호
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• pp.1852-1859
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• 2019

Chikungunya virus (CHIKV) is a single-stranded positive-sense RNA virus, belonging to the genus Alphavirus of the Togaviridae family. It causes multiple symptoms, including headache, fever, severe joint and muscle pain, and arthralgia. Since CHIKV was first isolated in Tanzania in 1952, there have been multiple outbreaks of chikungunya fever. However, its pathogenesis and mechanisms of viral immune evasion have been poorly understood. In addition, the exact roles of individual CHIKV genes on the host innate immune response remain largely unknown. To investigate if CHIKV-encoded genes modulate the type I interferon (IFN) response, each and every CHIKV gene was screened for its effects on the induction of the IFN-β promoter. Here we report that CHIKV nsP2, E2 and E1 strongly suppressed activation of the IFN-β promoter induced by the MDA5/RIG-I receptor signaling pathway, suggesting that nsP2, E2, and E1 are the major antagonists against induction of IFN-β. Delineation of underlying mechanisms of CHIKV-mediated inhibition of the IFN-β pathway may help develop virus-specific therapeutics and vaccines.

• 한국미생물학회:학술대회논문집
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• 한국미생물학회 2009년도 International Meeting of the Microbiological Society of Korea
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• pp.99-100
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• 2009

• IMMUNE NETWORK
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• 제21권4호
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• pp.27.1-27.12
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• 2021

Respiratory syncytial virus (RSV) is the leading cause of respiratory viral infection in infants and children. However, little is known about the contribution of monocytes to antiviral responses against RSV infection. We identified the IFN-β production of monocytes using IFN-β/YFP reporter mice. The kinetic analysis of IFN-β-producing cells in in vivo RSV-infected lung cells indicated that monocytes are recruited to the inflamed lung during the early phase of infection. These cells produced IFN-β via the myeloid differentiation factor 88-mediated pathway, rather than the TLR7- or mitochondrial antiviral signaling protein-mediated pathway. In addition, monocyte-ablated mice exhibited decreased numbers of IFN-γ-producing and RSV Ag-specific CD8⁺ T cells. Collectively, these data indicate that monocytes play pivotal roles in cytotoxic T-cell responses and act as type I IFN producers during RSV infection.

• Molecules and Cells
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• 제41권3호
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• pp.214-223
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• 2018

Oligoadenylate synthetase (OAS) protein family is the major interferon (IFN)-stimulated genes responsible for the activation of RNase L pathway upon viral infection. OAS-like (OASL) is also required for inhibition of viral growth in human cells, but the loss of one of its mouse homolog, OASL1, causes a severe defect in termination of type I interferon production. To further investigate the antiviral activity of OASL1, we examined its subcellular localization and regulatory roles in IFN production in the early and late stages of viral infection. We found OASL1, but not OASL2, formed stress granules trapping viral RNAs and promoted efficient RLR signaling in early stages of infection. Stress granule formation was dependent on RNA binding activity of OASL1. But in the late stages of infection, OASL1 interacted with IRF7 transcripts to inhibit translation resulting in down regulation of IFN production. These results implicate that OASL1 plays context dependent functions in the antiviral response for the clearance and resolution of viral infections.

• Journal of Ginseng Research
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• 제41권2호
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• pp.127-133
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• 2017

Background: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. Methods: The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis $factor-{\alpha}/interferon-{\gamma}-treated$ synovial cells, and HEK293 cells transfected with various inducers of inflammation. Results: G-Rc significantly inhibited the expression of macrophage-derived cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$. G-Rc also markedly suppressed the activation of TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells. Conclusion: G-Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling.

• Clinical and Experimental Pediatrics
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• 제53권2호
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• pp.136-145
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• 2010

Natural killer T (NKT) cell is a special type of T lymphocytes that has both receptor of natural killer (NK) cell (NK1.1, CD161c) and T cell (TCR) and express a conserved or invariant T cell receptor called $V{\alpha}14J{\alpha}18$ in mice or Va24 in humans. Invariant NKT (iNKT) cell recognizes lipid antigen presented by CD1d molecules. Marine-sponge-derived glycolipid, ${\alpha}-galactosylceremide$ (${\alpha}-GalCer$), binds CD1d at the cell surface of antigen-presenting cells and is presented to iNKT cells. Within hours, iNKT cells become activated and start to secrete Interleukin-4 and $interferon-{\gamma}$. NKT cell prevents autoimmune diseases, such as type 1 diabetes, experimental allergic encephalomyelitis, systemic lupus erythematous, inflammatory colitis, and Graves' thyroiditis, by activation with ${\alpha}-GalCer$. In addition, NKT cell is associated with infectious diseases by mycobacteria, leshmania, and virus. Moreover NKT cell is associated with asthma, especially CD4+ iNKT cells. In this review, I will discuss the characteristics of NKT cell and the association with inflammatory diseases, especially asthma.

• Molecules and Cells
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• 제45권4호
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• pp.257-272
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• 2022

In addition to inducing apoptosis, caspase inhibition contributes to necroptosis and/or autophagy depending on the cell type and cellular context. In macrophages, necroptosis can be induced by co-treatment with Toll-like receptor (TLR) ligands (lipopolysaccharide [LPS] for TLR4 and polyinosinic-polycytidylic acid [poly I:C] for TLR3) and a cell-permeable pan-caspase inhibitor zVAD. Here, we elucidated the signaling pathways and molecular mechanisms of cell death. We showed that LPS/zVAD- and poly I:C/zVAD-induced cell death in bone marrow-derived macrophages (BMDMs) was inhibited by receptor-interacting protein kinase 1 (RIP1) inhibitor necrostatin-1 and autophagy inhibitor 3-methyladenine. Electron microscopic images displayed autophagosome/autolysosomes, and immunoblotting data revealed increased LC3II expression. Although zVAD did not affect LPS- or poly I:C-induced activation of IKK, JNK, and p38, it enhanced IRF3 and STAT1 activation as well as type I interferon (IFN) expression. In addition, zVAD inhibited ERK and Akt phosphorylation induced by LPS and poly I:C. Of note, zVAD-induced enhancement of the IRF3/IFN/STAT1 axis was abolished by necrostatin-1, while zVAD-induced inhibition of ERK and Akt was not. Our data further support the involvement of autocrine IFNs action in reactive oxygen species (ROS)-dependent necroptosis, LPS/zVAD-elicited ROS production was inhibited by necrostatin-1, neutralizing antibody of IFN receptor (IFNR) and JAK inhibitor AZD1480. Accordingly, both cell death and ROS production induced by TLR ligands plus zVAD were abrogated in STAT1 knockout macrophages. We conclude that enhanced TRIF-RIP1-dependent autocrine action of IFNβ, rather than inhibition of ERK or Akt, is involved in TLRs/zVAD-induced autophagic and necroptotic cell death via the JAK/STAT1/ROS pathway.

• Journal of Animal Science and Technology
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• 제51권6호
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• pp.471-484
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• 2009

The peri-implantation period in mammals is critical with respect to survival of the conceptus (embryo/fetus and associated extraembryonic membranes) and establishment of pregnancy. During this period of pregnancy, reciprocal communication between ovary, conceptus, and endometrium is required for successful implantation and placentation. At this time, interferon tau (IFNT) is synthesized and secreted by the mononuclear trophectodermal cells of the conceptus between days 10 and 21~25. The actions of IFNT to signal pregnancy recognition and induce or increase expression of IFNT-stimulated genes (ISGs), such as ISG15 and OAS, are mediated by the Type I IFN signal transduction pathway. This article reviews the history, signaling pathways of IFNT and the uterine expression of several IFNT-stimulated genes during the peri-implantation period. Collectively, these newly identified genes are believed to be critical to unraveling the mechanism(s) of reciprocal fetal-maternal interactions required for successful implantation and pregnancy.