<i>Pseudomonas aeruginosa</i> Eliminates Natural Killer Cells via Phagocytosis-Induced Apoptosis

Chung, Jin Woong,Piao, Zheng-Hao,Yoon, Suk Ran,Kim, Mi Sun,Jeong, Mira,Lee, Suk Hyung,Min, Jeong Ki,Kim, Jae Wha,Cho, You-Hee,Kim, Jin Chul,Ahn, Jeong Keun,Kim, Kyoon Eon,Choi, Inpyo Public Library of Science 2009 PLoS pathogens Vol.5 No.8

<▼1><P><I>Pseudomonas aeruginosa</I> (PA) is an opportunistic pathogen that causes the relapse of illness in immunocompromised patients, leading to prolonged hospitalization, increased medical expense, and death. In this report, we show that PA invades natural killer (NK) cells and induces phagocytosis-induced cell death (PICD) of lymphocytes. <I>In vivo</I> tumor metastasis was augmented by PA infection, with a significant reduction in NK cell number. Adoptive transfer of NK cells mitigated PA-induced metastasis. Internalization of PA into NK cells was observed by transmission electron microscopy. In addition, PA invaded NK cells via phosphoinositide 3-kinase (PI3K) activation, and the phagocytic event led to caspase 9-dependent apoptosis of NK cells. PA-mediated NK cell apoptosis was dependent on activation of mitogen-activated protein (MAP) kinase and the generation of reactive oxygen species (ROS). These data suggest that the phagocytosis of PA by NK cells is a critical event that affects the relapse of diseases in immunocompromised patients, such as those with cancer, and provides important insights into the interactions between PA and NK cells.</P></▼1><▼2><P><B>Author Summary</B></P><P>Phagocytic leukocytes, including neutrophils and macrophages, are critical for innate immunity against invading bacteria. Binding and internalization of bacteria by these immune cells stimulates a variety of anti-microbial activities. Although the immune cells are specialized for elimination of bacteria, cellular apoptosis by bacterial phagocytosis has emerged as an important mechanism of pathogenesis. NK cells are non-phagocytic lymphocytes that are responsible for innate immunity via elimination of virus or bacteria-infected cells, as well as transformed cells. We found that PA invades NK cells and that this phagocytic event results in the generation of ROS within the NK cells, leading to apoptosis. The elimination of NK cells, at least in part, may be responsible for the relapse in PA-infected cancer patients. Based on these findings, studies on the interactions between bacterial determinants and host receptors should provide further insight into the mechanisms of bacterial pathogenesis.</P></▼2>

Thioredoxin-interacting protein regulates hematopoietic stem cell quiescence and mobilization under stress conditions.

Jeong, Mira,Piao, Zheng-Hao,Kim, Mi Sun,Lee, Suk Hyung,Yun, Sohyun,Sun, Hu-Nan,Yoon, Suk Ran,Chung, Jin Woong,Kim, Tae-Don,Jeon, Jun Ho,Lee, Jiwon,Kim, Hyun-Nam,Choi, Je-Yong,Choi, Inpyo Williams Wilkins 2009 JOURNAL OF IMMUNOLOGY Vol.183 No.4

<P>Hematopoietic stem cells (HSCs) are maintained in a quiescent state in bone marrow (BM) niches by intrinsic and extrinsic signals. The mechanisms regulating the quiescence and mobilization of HSCs, however, remain unclear. In this study, we report that the expression of thioredoxin-interacting protein (TXNIP) is decreased during HSC activation. In Txnip(-/-) mice, the long-term reconstituting HSC population is decreased and exhausted, and its capacity to repopulate is rapidly lost. These effects are associated with hyperactive Wnt signaling, an active cell cycle, and reduced p21 expression under conditions of stress. TXNIP deficiency reduced the CXCL12- and osteopontin-mediated interaction between HSCs and the bone marrow, and impaired homing and retention in the osteoblastic niche, resulting in mobilized HSCs. Therefore, we propose that TXNIP is essential for maintaining HSC quiescence and the interaction between HSCs and the BM niche.</P>

Distinctive bone regeneration of calvarial defects using biphasic calcium phosphate supplemented ultraviolet-crosslinked collagen membrane

Hong, Inpyo,Khalid, Alharthi Waleed,Pae, Hyung-Chul,Cha, Jae-Kook,Lee, Jung-Seok,Paik, Jeong-Won,Jung, Ui-Won,Choi, Seong-Ho Korean Academy of Periodontology 2020 Journal of Periodontal & Implant Science Vol.50 No.1

Purpose: To overcome several drawbacks of chemically-crosslinked collagen membranes, modification processes such as ultraviolet (UV) crosslinking and the addition of biphasic calcium phosphate (BCP) to collagen membranes have been introduced. This study evaluated the efficacy and biocompatibility of BCP-supplemented UV-crosslinked collagen membrane for guided bone regeneration (GBR) in a rabbit calvarial model. Methods: Four circular bone defects (diameter, 8 mm) were created in the calvarium of 10 rabbits. Each defect was randomly allocated to one of the following groups: 1) the sham control group (spontaneous healing); 2) the M group (defect coverage with a BCP-supplemented UV-crosslinked collagen membrane and no graft material); 3) the BG (defects filled with BCP particles without membrane coverage); and 4) the BG+M group (defects filled with BCP particles and covered with a BCP-supplemented UV-crosslinked collagen membrane in a conventional GBR procedure). At 2 and 8 weeks, rabbits were sacrificed, and experimental defects were investigated histologically and by micro-computed tomography (micro-CT). Results: In both micro-CT and histometric analyses, the BG and BG+M groups at both 2 and 8 weeks showed significantly higher new bone formation than the control group. On micro-CT, the new bone volume of the BG+M group (48.39±5.47 ㎣) was larger than that of the BG group (38.71±2.24 ㎣, P=0.032) at 8 weeks. Histologically, greater new bone area was observed in the BG+M group than in the BG or M groups. BCP-supplemented UV-crosslinked collagen membrane did not cause an abnormal cellular reaction and was stable until 8 weeks. Conclusions: Enhanced new bone formation in GBR can be achieved by simultaneously using bone graft material and a BCP-supplemented UV-crosslinked collagen membrane, which showed high biocompatibility and resistance to degradation, making it a biocompatible alternative to chemically-crosslinked collagen membranes.

Adiponectin Deficiency Suppresses Lymphoma Growth in Mice by Modulating NK Cells, CD8 T Cells, and Myeloid-Derived Suppressor Cells

Han, Sora,Jeong, Ae Lee,Lee, Sunyi,Park, Jeong Su,Kim, Kwang Dong,Choi, Inpyo,Yoon, Suk Ran,Lee, Myung Sok,Lim, Jong-Seok,Han, Seung Hyun,Yoon, Do Young,Yang, Young The American Association of Immunologists, Inc. 2013 JOURNAL OF IMMUNOLOGY Vol.190 No.9

<P>Previously, we found that adiponectin (APN) suppresses IL-2–induced NK cell activation by downregulating the expression of the IFN-γ–inducible TNF-related apoptosis-inducing ligand and Fas ligand. Although the antitumor function of APN has been reported in several types of solid tumors, with few controversial results, no lymphoma studies have been conducted. In this study, we assessed the role of APN in immune cell function, including NK cells, CTLs, and myeloid-derived suppressor cells, in EL4 and B16F10 tumor-bearing APN knockout (KO) mice. We observed attenuated EL4 growth in the APNKO mice. Increased numbers of splenic NK cells and splenic CTLs were identified under naive conditions and EL4-challenged conditions, respectively. In APNKO mice, splenic NK cells showed enhanced cytotoxicity with and without IL-2 stimulation. Additionally, there were decreased levels of myeloid-derived suppressor cell accumulation in the EL4-bearing APNKO mice. Enforced MHC class I expression on B16F10 cells led to attenuated growth of these tumors in APNKO mice. Thus, our results suggest that EL4 regression in APNKO mice is not only due to an enhanced antitumor immune response but also to a high level of MHC class I expression.</P>

차량용 멀티미디어 디바이스를 위한 적외선 방식 모션인식 중앙 조작계 개발

이규환(Kyuhwan Lee),정이화(Leehwa Jeong),경태호(Taeho Kyung),홍인표(Inpyo Hong),민한음(Hanum Min) 한국자동차공학회 2011 한국자동차공학회 부문종합 학술대회 Vol.2011 No.5

Recently, IT industry is in fast growth. And very much IT convenient device for life is developed. This has been emerged as core technology in automotive industries. And some of these products have unintended malfunctions. because of the environment of driving, the device can cause a driver’s momentary carelessness. And this carelessness can cause a traffic accident. Wierwille & Tijerina(1996) studied about car crash in North Carolina. In study, a driver’s carelessness accident is 55.5% of 2,819 accidents. This result means accident can be happen by ordinary action like changing channel of radio. So, many people are studing a simple control method. This paper suggests this control method using IR sensor. The method can simply control increased devices. And It can decrease carelessness action for safe drive. Used IR sensor gets 3 IR LED data. The 3 IR LED is used to recognize hand motion like directions of right, left, up and down. These motions are used to control devices like radio, MP3, navigation. This is more safer control than before because this needs not to find the controller’s location exactly.

MATLAB의 Auto code generation과 Verification 기능을 이용한 자동차 실내램프 시스템 검증에 관한 연구

이규환(Kyuhwan Lee),정이화(Leehwa Jeong),경태호(Taeho Kyung),홍인표(Inpyo Hong),구자용(Jaryong Ku) 한국자동차공학회 2010 한국자동차공학회 학술대회 및 전시회 Vol.2010 No.11

Recently, Software design is developed by regular procedures. But these regular procedures are difficult to fulfill in the field. The field can be changed the project in coding or test step by the change of requirements or the occurrence of a problem. Model-Based Design is proposed this problem solution. Model-Based Design is recycled in various stages of design information. So, the design method can be modeling and simulation before to the real hardware. This Model-Based Design’s typical program is the MATLAB. The interior lamp of automotive is developed very much. Recent interior lamp is not simple. The interior lamp functions are only lamp ON or OFF function but also CAN communication, Data processing, Input processing, analysis and results output function. This function is working used MCU(microcontroller unit). Also center fascia is have very many function. So, this place can’t add function. For that reason, interior lamp is including something of user indirect control like bluetooth module. Reliability is important in interior lamp because of this complicated function. And this reliability of products raises the commercial value. So this paper is suggested development method of interior lamp system using MATLAB.

Osteopontin Promotes the Development of Natural Killer Cells from Hematopoietic Stem Cells

Chung, Jin Woong,Kim, Mi Sun,Piao, Zheng-Hao,Jeong, Mira,Yoon, Suk Ran,Shin, Nara,Kim, Sang Yong,Hwang, Eun Sook,Yang, Young,Lee, Young Ho,Kim, Young Sang,Choi, Inpyo Wiley (John WileySons) 2008 Stem Cells Vol.26 No.8

<P>The detailed mechanisms driving the development of natural killer (NK) cells from hematopoietic stem cells remain to be clearly elucidated. Here, we show that osteopontin (OPN) is a key factor for NK development. OPN-deficient mice evidenced severe impairments of NK development in bone marrow (BM) and spleen in which the NK populations that express CD122 and NK cell receptors were reduced. However, the absence of intrinsic OPN expression did not affect NK development, whereas the absence of OPN in the microenvironment caused a significant reduction in NK population. The expression of OPN was induced by interleukin (IL)-15 in BM stromal cells, and the defect in NK differentiation in IL-15(-/-) hematopoietic precursor cells (HPC) was recovered by addition of recombinant OPN, suggesting that the microenvironmental OPN may be a key factor in IL-15-mediated NK differentiation. In addition, OPN-driven NK maturation was reduced in T-bet-deficient HPC, suggesting that T-bet is required for OPN-mediated NK development. Collectively, these results show that paracrine OPN signaling drives NK-lineage commitment, thus ultimately promoting NK cell development. Disclosure of potential conflicts of interest is found at the end of this article.</P>

백혈병 마우스 모델의 동종골수이식에서 활성화된 자연살해세포들의 보충이 이식편대백혈병효과와 이식편대숙주반응에 미치는 영향

엄현석,한치화,박수정,김소연,정낙균,정대철,진종률,최일봉,양형모,서영훈,송현근,최인표,민우성,김춘추 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

배경: 백혈병에서 동종골수이식 (allogeneic bone marrow transplantation)의 성공적 치료 효과를 얻기 위해서는 이식편대숙주반응 (graft-versus-host disease, GVHD) 발생의 극복과 재발의 방지가 중요한 과제이다. 골수를 역류원심성 세포분리 (counterflow centrifugal elutriation, CCE) 방법으로 분리하여 얻은 rotor off (R/O) 세포분획은 T 세포의 수는 적지만 조혈모세포들을 다량 포함하고 있어 동종골수이식에서 주조직적합복합체 (major histocompatibility complex, MHC) 차이를 극복할 수 있고, 이식편의 생착 성공과 GVHD 발생 예방에 효과적이다. 그러나 골수로부터 T 세포를 제거하면 백혈병세포를 공격하는 이식편대백혈병 (graft-versus-leukemia, GVL) 효과가 감소되기 때문에 백혈병 재발의 빈도가 높다. 자연살해세포 (natural killer cell, NK cell)의 보충 첨가는 동종골수이식 후 GVHD 발생을 줄이면서 충분한 GVL 효과를 얻을 수가 있다. 따라서 저자는 분리 후 IL-2로 활성화시킨 NK 세포들을 골수 R/O 세포분획과 함께 백혈병 마우스 모델에 동종이식함으로써 GVHD와 GVL에 미치는 효과를 관찰하였다. 방법: Balb/c (H-2^(d)) 마우스에서 유래된 A20 (murine B-lymphoma/leukemia cell line, H-2^(d)) 백혈병 세포를 이식 2 일 전에 Balb/c 마우스에 주입하고, 치사량의 전신 방사선을 조사한 직후에 Balb/c 또는 C57BL/6 (H-2^(b)) 마우스의 골수 R/O 세포분획을 꼬리정맥을 통하여 주입하였다. 이들은 모두 이식 후 6-8 주 이내에 사망하였다. 동종이식의 대조군 (n=9)에는 1 × 10^(7)의 R/O 세포분획만을 주입하였고, 실험군 (n=9)에는 C57BL/6 마우스의 비장세포들로부터 단클론항체들을 이용한 negative selection방법으로 분리한 후 IL-2로 활성화된 5 × 10^(5)의 NK 세포분획을 1 × 10^(7)의 R/O 세포분획과 함께 주입하였다. GVL 효과의 판정은 이식 후 14 일과 28 일 째 되는 날 마우스에서 골수, 비장, 간 등을 얻어 백혈병 세포들의 침윤을 조직학적으로 관찰하였으며, GVHD의 정도는 육안적 관찰법으로 평가하였다. 결과: R/O 세포분획만을 이식한 대조군의 골수, 비장, 그리고 간 조직에서는 A20 백혈병 세포의 침윤이 각각 89% (8/9), 78% (7/9)와 22% (2/9)에서 관찰되었고, R/O 세포분획과 NK 세포분획을 함께 이식한 실험군에서는 비장과 간을 제외한 골수에서만 89% (8/9)에서 A20 백혈병 세포의 침윤이 관찰되어 두 군 사이에 장기별 분포의 차이를 볼 수 있었다 (P= 0.0001). 한편 GVHD는 두 군 모두에서 경하게 나타나서 유의한 차이는 없었다. 또한 생착 부전으로 사망한 마우스는 없었다. 결론: CCE를 이용하여 T 세포를 제거한 동종골수이식에서 NK 세포의 보충은 GVHD의 악화는 일으키지 않으면서, 백혈병의 진행을 억제하는 GVL 효과를 얻을 수 있었다. Background: Allogeneic bone marrow transplantation (BMT) with T cell-depleted marrow accompanies engraftment failure and relapse of leukemia by a loss of the graft-versus-leukemia (GVL) effect frequently, while it can prevent GVHD. Supplement of NK cells could prevent GVHD and enhance GVL effect in several murine allogeneis BMT models Roter off (R/O) cell fraction obtained by counterflow centriation elutriatio (CCO) contains small number of T cells and many hematopoietic stem cells. The aim of this study was to determine the effect of R/O cell fraction supplemented with IL-2 activated NK cells on GVL and GVHD within the leukemic mouse BMT model. Methods: Inoculation of A20 (H-2d, murine B-lymphoma/leukemia, Balb/c origin) cells into Balb/c mice via the tail vein 2 days prior to lethal total body irradiation (TBI) and infusion of the Balb/c BM or C57BL/6 (H-2b) R/O fraction were performed. It resulted in 100% mortality within 6 to 8 weeks. The irradiated mice in the control group were injected with 1 × 107 R/O cell fraction alone (n=9) and in the experimental group mice were injected with 1 × 107 R/O cell fraction plus 5 × 105 negatively selected IL-2 activated NK cell fractions of the spleens via the tail vein (n=9). On day 14 and 28 after BMT, the bone marrows, spleens, and livers of mice were harvested for histopathologic analysis of the infiltrations of leukemic cells. We then evaluated the GVHD within the mice. Results: A histopathologic study of the recipients receiving R/O fraction alone showed infiltration of leukemic cells, 89% (8/9) in bone marrows, 78% (7/8) in spleens, and 22% (2/9) in livers. The experimental group of mice showed only the infiltration of leukemic cells 89% (8/9) in bone marrows, not in spleens and livers. There were the organ differences of the leukemic cells infiltrations between the two groups (P=0.0001). There were no obvious differences in the GVHD scores between these two groups, and severe GVHD was not observed. There was no engraftment failure among groups. Conclusion: Thus, our findings suggest that R/O cell fraction obtained by CCE and supplemented with NK cells can promote GVL effect without mediating clinically overt GVHD in allogeneic BMT of mouse leukemia.

IL-17A and Th17 Cells Contribute to Endometrial Cell Survival by Inhibiting Apoptosis and NK Cell Mediated Cytotoxicity of Endometrial Cells via ERK1/2 Pathway

Kang Young-Ju,Cho Hee Jun,Lee Yunhee,Park Arum,Kim Mi Jeong,Jeung In Cheul,Jung Yong-Wook,Jung Haiyoung,Choi Inpyo,Lee Hee Gu,Yoon Suk Ran 대한면역학회 2023 Immune Network Vol.23 No.2

Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.

3DCA제작을 통한 Vac-Lock 사용시 효율성향상에 대한 연구

이영철,이철빈,강노현,김동욱,이중용,정인표,Lee YoungChul,Lee ChulBin,Kang NoHyun,Kim DongEuk,Lee JungYong,Jeong InPyo 대한방사선치료학회 2004 大韓放射線治療技術學會誌 Vol.16 No.1

목 적 : 본원에서는 Whole body용 Vac-Lock을 이용하여 환자의 전신체형을 뜨고 있다. 그러나 몇 가지 애로사항이 발생하여 본 연구에서는 이러한 문제점을 찾아 보고, 애로사항을 해결하고자 자체 제작한 3DCA에 대해 알아보고자 한다. 대상 및 방법 : 본원에서 사용중인 Whole body용 Vac-Lock의 크기는 2종류가 있는데, 그에 따라 제작한 3DCA를 제작하는데 재질은 목재를 이용하였는데, 그것은 비용절감과 직접 제작을 하기 위해서는 쉽게 재질을 다룰 수 있고, 모양을 내기 위해서는 목재가 적정하였다고 사료되었다. 결 과 : Vac-Lock을 사용하면서 애로사항을 4가지로 분석하였고, 이러한 문제점을 해결하기 위해 3DCA를 제작 사용하게 되었다. 첫 번째 문제는 많은 제작 인원으로, 3DCA를 사용하여 전에는 환자의 전신체형을 뜨는데 5명 내지 6명이 동원 되었는데, 이제는 한사람이 할 수 있게 되었다. 두 번째는 제작 시간으로 3DCA를 사용하기 전에는 많은 인원이 동원되어도 1시간 이상이 소요되었으나, 이제는 한사람이 10분 이내로 단축할 수 있었다. 세 번째는 Vac-Lock이 큰 관계로 체형을 뜬 후 치료기기와 충돌하는 경우가 있었으나, 지금은 그러한 현상을 방지할 수 있었다. 네 번째로 3DCA를 사용하기 전에는 Vac-Lock의 외형이 깔끔하지 못했는데, 이제는 매끄럽게 체형을 뜰 수가 있었다. 결 론 : 환자가 치료받은 자세를 치료시 마다 동일하게 유지하기 위해 Vac-Lock을 사용하였는데, Vac-Lock 제품의 특성상 사용시 조금한 불편함이 근무자에게 애로사항으로 다가왔다. 이번 연구도 그러한 불편함을 조금이나마 줄여 보고자 하였고, 실제 문제점을 찾아 보고, 그 문제점을 해결하고자 3DCA를 제작 사용하였는데 많은 효과를 보고 있다. Purpose : Patient immobilization is crucial factor for radiation therapy. Generally, we have been used vacuum bag immobilization device(Vac-Lock) for whole body immobilization. In order to easily set up of vacuum bag(Vac-Lock), we made a 3DCA(3-Dimensional Conformal Accessary). The purpose of this study is evaluation of effectiveness of 3DCA using Vack-Lock for patient immobilization. Materials and Methods : We made 3DCA(3-Dimensional Conformal Accessary) tool of wooden boards. The reasons to choice of wooden boards are its easily handling nature and cheap expenses. Results : (1) We reduced man power from $5{\sim}6$persons to 1person to make immobilizations, (2) Shortened work time from 1hour to within 10minutes. (3) Avoid a collision to treatment gantry head. (4) Its shapes are smart and clean. Conclusion : We have made and used 3DCA(3-Dimensional Conformal Accessary) tool was very effective and convenience for the patients and users.