Tissue transglutaminase-interleukin-6 axis facilitates peritoneal tumor spreading and metastasis of human ovarian cancer cells

오근희,문형곤,이동섭,유영복 한국실험동물학회 2015 Laboratory Animal Research Vol.31 No.4

Inflammation has recently been implicated in cancer formation and progression. As tissue transglutaminase (TG2) has been associated with both inflammatory signaling and tumor cell behavior, we propose that TG2 may be an important link inducing interleukin-6 (IL-6)-mediated cancer cell aggressiveness, including cancer stem cell-like characteristics and distant hematogenous metastasis. We evaluated the effect of differential TG2 and IL-6 expression on in vivo distant metastasis of human ovarian cancer cells. IL-6 production in human ovarian cancer cells was dependent on their TG2 expression levels. The size and efficiency of tumor sphere formation were correlated with TG2 expression levels and were dependent on TG2-mediated IL-6 secretion in human ovarian cancer cells. Primary tumor growth and propagation in the peritoneum and distant hematogenous metastasis into the liver and lung were also dependent on TG2 and downstream IL-6 expression levels in human ovarian cancer cells. In this report, we provide evidence that TG2 is an important link in IL-6-mediated tumor cell aggressiveness, and that TG2 and downstream IL-6 could be important mediators of distant hematogenous metastasis of human ovarian cancer cells. Intervention specific to TG2 and/or downstream IL-6 in ovarian cancer cells could provide a promising means to control tumor metastasis.

Maturation-Resistant Dendritic Cells Ameliorate Experimental Autoimmune Uveoretinitis

오근희,김연수,이동섭 대한면역학회 2011 Immune Network Vol.11 No.6

Background: Endogenous uveitis is a chronic inflammatory eye disease of human, which frequently leads to blindness. Experimental autoimmune uveoretinitis (EAU) is an animal disease model of human endogenous uveitis and can be induced in susceptible animals by immunization with retinal antigens. EAU resembles the key immunological characteristics of human disease in that both are CD4^+ T-cell mediated diseases. Dendritic cells (DCs) are specialized antigen-presenting cells that are uniquely capable of activating naïve T cells. Regulation of immune responses through modulation of DCs has thus been tried extensively. Recently our group reported that donor strain-derived immature DC pretreatment successfully controlled the adverse immune response during allogeneic transplantation. Methods: EAU was induced by immunization with human interphotoreceptor retinoid-binding protein (IRBP) peptide1-20. Dendritic cells were differentiated from bone marrow in the presence of recombinant GM-CSF. Results: In this study, we used paraformaldehyde-fixed bone marrow-derived DCs to maintain them in an immature state. Pretreatment with fixed immature DCs, but not fixed mature DCs, ameliorated the disease progression of EAU by inhibiting uveitogenic CD4^+ T cell activation and differentiation. Conclusion: Application of iBMDC prepared according to the protocol of this study would provide an important treatment modality for the autoimmune diseases and transplantation rejection.

CP-690550 Treatment Ameliorates Established Disease and Provides Long-Term Therapeutic Effects in an SKG Arthritis Model

오근희,Myung Won Seo,In Gyu Kim,Young-il Hwang,Hee-Yoon Lee,이동섭 대한면역학회 2013 Immune Network Vol.13 No.6

Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5∼4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-γ, and IL-6 and increased level of immunoregulatory IL-10.

스테로이드와 TNF에 의한 항원 비특이적 미성숙 흉선세포 사멸

오근희,이동섭,서동철,조재진 대한면역학회 2004 Immune Network Vol.4 No.2

Background: In the thymus, developing thymocytes continually interact with thymic epithelial cell components. Self MHC restriction of mature T cells are imposed in the thymus through interaction of immature double positive thymocytes and thymic cortical epithelial cells. The site of negative selection, however, is a matter of debate. Through systemic injection of anti-TCR antibody or antigenic peptides, investigators suggested that most of the negative selection occurs in the thymic cortex. But the requirements for negative selection, i.e cellular counterparts and costimulatory molecules are more available in the medulla or cortico-medullary junction rather than in the thymic cortex. Methods: The direct and indirect pathways of thymocyte death after systemic anti-TCR antibody injection were separated through several experimental systems. B6 mice were either adrenalectomized or sham-adrenalectomized to evaluate the role of endogenous glucocorticoids from adrenal gland. Role of TNF were evaluated through using TNF receptor double knockout mice. Results: We found that without indirectly acting mediators such as TNF-α or corticosteroid, double positive thymocyte death were minimal by systemic injection of anti-TCR antibody in TNF receptor double knockout neonatal mice. Also by analyzing neonatal wild-type mice with adoptively transferred mature T cells, only peripheral activation of mature T cells could induce extensive double positive thymocyte death. Conclusion: Thus, systemically injected anti-TCR antibody mediated thymocyte death are mostly induced through indirect pathway. (Immune Network 2004;4(2):81-87)

Osteopontin Potentiates Pulmonary Inflammation and Fibrosis by Modulating IL-17/IFN-γ-secreting T-cell Ratios in Bleomycin-treated Mice

오근희,서명원,김영환,이동섭 대한면역학회 2015 Immune Network Vol.15 No.3

Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPNdeficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of CD4+ αβ T cells and IL-17-producing γδ T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of CD4+ αβ T cells and the percentage of IFN-γ-producing γδ T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in CD4+ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-γ T cells.

스포츠 수영에 관하여

오근희 한국공학교육학회 2001 Ingenium(人材니움) Vol.8 No.3

Murine Sca1+Lin− bone marrow contains an endodermal precursor population that differentiates into hepatocytes

오근희,손서연,서명원,이학모,오주은,최은영,이동섭,박경수 생화학분자생물학회 2015 Experimental and molecular medicine Vol.47 No.-

The direct differentiation of hepatocytes from bone marrow cells remains controversial. Several mechanisms, including transdifferentiation and cell fusion, have been proposed for this phenomenon, although direct visualization of the process and the underlying mechanisms have not been reported. In this study, we established an efficient in vitro culture method for differentiation of functioning hepatocytes from murine lineage-negative bone marrow cells. These cells reduced liver damage and incorporated into hepatic parenchyma in two independent hepatic injury models. Our simple and efficient in vitro protocol for endodermal precursor cell survival and expansion enabled us to identify these cells as existing in Sca1+ subpopulations of lineage-negative bone marrow cells. The endodermal precursor cells followed a sequential developmental pathway that included endodermal cells and hepatocyte precursor cells, which indicates that lineage-negative bone marrow cells contain more diverse multipotent stem cells than considered previously. The presence of equivalent endodermal precursor populations in human bone marrow would facilitate the development of these cells into an effective treatment modality for chronic liver diseases.

스포츠 : 수영에 관하여

오근희 한국공학교육학회 ( 구 한국공학기술학회 ) 2001 공학교육동향 Vol.8 No.3

대학생의 개인적 특성에 따른 레저 스포츠 참여

오근희(Keun Hee Oh),김경렬(Kyuang Ryeal Kim) 한국여가레크리에이션학회 2000 한국여가레크리에이션학회지 Vol.19 No.-

수영 스포츠 참여와 심리적 웰빙에 관한 연구

오근희 ( Keun Hee Oh ),배상운 ( Sang Woon Bae ),강성웅 ( Sung Woong Kang ) 고려대학교 스포츠과학연구소 2010 스포츠科學論叢 Vol.16 No.-

본 연구는 많은 현대인들이 참여하고 있으며, 향후에도 참여하고 싶은 운동 종목 1위인 수영 스포츠 참여와 심리적 웰빙은 어떠한 관계가 있는지를 밝히는 것에 본 연구의 목적이 있다. 본 연구는 다음과 같은 결론을 도출하였다. 첫째, 수영 스포츠 참여에 따라 심리적 웰빙 자각 증세는 차이가 있다, 둘째, 수영 스포츠 참여에 따라 심리적 웰빙 하위 요인은 차이가 있다. 셋째, 심리적 웰빙 자각 증세에 따라 심리적 웰빙 하위 요인은 차이가 있다. 넷째, 심리적 웰빙 하위 요인은 심리적 웰빙 자각 증세에 영향을 미치고 있다. This study involves numbers of modem people as participants, placing its purpose on learning how psychological well-being correlates with the people engaging in swimming sports where swimming has been voted as no.1 sport for "most likely to continue in future". Conclusion on this research drew the following results: 1.Symptom of psychological well-being self-awareness differs depending on swimming sports participation scale. 2.Subordinate cause of psychological well-being differs depending on swimming sports participation scale. 3.Subordinate cause of psychological well-being differs depending on symptom of psychological well-being self-awareness. 4.Subordinate cause of psychological well-being has influence over symptom of psychological well-being self-awareness.