Interferon-γ Inhibits in vitro Mobilization of Eosinophils by Interleukin-5

Park, Choon-Sik,Choi, Eun Nam,Kim, Jung Sun,Choi, Yun Sung,Rhim, Tai Youn,Chang, Hun Soo,Chung, Il Yup S. Karger AG 2005 International archives of allergy and immunology Vol.136 No.3

<P><I>Background:</I> Th2 cytokines play pivotal roles in allergic inflammation, including eosinophilia, and their actions are antagonized by Th1 cytokines, conferring them therapeutic potential. <I>Methods:</I> In this study, we examined the ability of a number of cytokines to suppress the activation of eosinophils that function as effector cells for allergic airway diseases. <I>Results:</I> Interleukin (IL)-5, IL-6, and tumor necrosis factor (TNF) induced an eosinophil shape change, whereas interferon (IFN)-γ significantly inhibited the shape change. Other cytokines, including IL-1β, IL-4, IL-10 and IL-13, had little or only slightly enhancing or reducing effects on the shape change. We further analyzed the IFN-γ effect, showing that pretreatment with IFN-γ strongly suppressed IL-5-induced eosinophil shape change, and cycloheximide (CHX) abrogated the suppression by IFN-γ, suggesting that new protein synthesis is required for the inhibitory effect by this cytokine. In agreement with these results, IFN-γ blocked the eosinophil migration and ERK phophorylation induced by IL-5, and the addition of CHX restored eosinophil chemotaxis. <I>Conclusions:</I> Collectively, IFN-γ may attenuate eosinophilic inflammation by directly negating eosinophil mobilization.</P><P>Copyright © 2005 S. Karger AG, Basel</P>

주조직적합항원이 불일치하는 마우스 동종 조혈모세포이식에서 IL-2로 유도된 CD4+CD25+ T세포를 이용한 이식편대숙주병의 억제

현재호,정대철,정낙균,박수정,민우성,김태규,최병옥,김원일,한치화,김학기,Hyun, Jae Ho,Jeong, Dae Chul,Chung, Nak Gyun,Park, Soo Jeong,Min, Woo Sung,Kim, Tai Gyu,Choi, Byung Ock,Kim, Won Il,Han, Chi Wha,Kim, Hack Ki 대한면역학회 2003 Immune Network Vol.3 No.4

Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

Effects of <i>Ecklonia cava</i> ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: Role of suppressor of cytokine signaling

Kim, Se-Kwon,Lee, Da-Young,Jung, Won-Kyo,Kim, Ji-Hye,Choi, Inhak,Park, Sae-Gwang,Seo, Su-Kil,Lee, Soo-Woong,Lee, Chang Min,Yea, Sung Su,Choi, Yung Hyun,Choi, Il-Whan Elsevier 2008 BIOMEDICINE AND PHARMACOTHERAPY Vol.62 No.5

<P><B>Abstract</B></P><P><I>Ecklonia cava</I> (EC) is a brown alga that evidences radical scavenging activity, bactericidal activity, tyrosinase inhibitory activity, and protease inhibitory activity. However, its anti-allergic effects remain poorly understood. In the current study, we attempted to determine whether pretreatment with EC induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and airway luminal narrowing; the development of airway hyperresponsiveness; the detection of tumor necrosis factor-alpha (TNF-α) and Th2 cytokines, including IL-4 and IL-5 in the bronchoalveolar lavage (BAL) fluid; and the detection of allergen-specific immunoglobulin E (IgE) in the serum. However, the administration of EC extract prior to the final airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that EC extracts treatment resulted in significant reductions on matrix metalloproteinase-9 (MMP-9) and Suppressor of cytokine signaling-3 (SOCS-3) expression and a reduction in the increased eosinophil peroxidase (EPO) activity. The treatment of animals with EC extracts resulted in a significant reduction in the concentrations of the Th2 cytokine (IL-4 and IL-5) in the airways, without any concomitant increase in the concentration of Th1 cytokines. These findings indicate that EC extracts may prove useful as an adjuvant therapy for allergic airway reactions via the inhibition of the Th2 response. Accordingly, this study may provide evidence that EC extract performs a critical function in the amelioration of the pathogenetic process of asthma in mice.</P>

Bis(p-substituted phenyl) 2-decyloxyterephthalate의 액정 특성에 대한 치환기 효과

박주훈,이종규,최옥병,소봉근,이수민,이준우,진정일,Park, Joo-Hoon,Lee, Jong-Kyu,Choi, Ok-Byung,So, Bong-Keun,Lee, Soo-Min,Lee, Jun-Woo,Jin, Jung-Il 대한화학회 2000 대한화학회지 Vol.44 No.2

Eleven new compounds that are composed of bis(p-substituted phenyl) terephthalate unitand the decyloxy pendant as lateral were synthesized and their thermal and liquid crystalline properties were studied by the differential scanning calorimetry (DSC) and on a hot-stage of a polarizing microscope. The ter-minal substituent groups of the compound were varied; X= -H(II-H), -F(lI-F), -CII(II-CI), -Br(ll-Br), -I(II-I), -$NO_2(lI-NO_2$), $-CF_3(II-CF_3$), -$OC_2H_5(II-OC_2H_5$), -$OC_4H_9(II-OC_4H_9$), -$C_6H_5(Il-C_6H_5$). The compounds of $II-OC_2H_5,\;II-OC_4H_9$ and $II-C_6H_5$ were monotropically nematic. In contrast, the compounds of Il-H, II-F, II-Cl, II-Br, II-I, $lI-NO_2$, $II-CF_3$, and II-CN did not show liquid crystalline properties. 비스(파라-치환페닐)테레프탈산 에스테르의 중앙 테레프탈산 벤젠고리 측면에 데실옥시기가 결합하고 있는 열한개의 새로운 화합물을 합성하였고, 이들의 열적 및 액정 성질을 DSC와 가열판이 부착된 편광현미경을 사용하여 조사하였다. 메소겐의 말단 치환기 X= -H(II-H), -F(II-F), -Cl(Il-Cl), -Br(Il-Br), -I(II-I), -$NO_2(lI-NO_2$), $-CF_3(II-CF_3$), -$OC_2H_5(II-OC_2H_5$), -$OC_4H_9(II-OC_4H_9$), -CN(II-CN) 및 -$C_6H_5(Il-C_6H_5$)로 바꾸었다. $II-OC_2H_5,\;II-OC_4H_9$, 및 $II-C_6H_5$는 단방성 네마틱 액정이었으며, II-H, lI-F, II-Cl, Il-Br, II-I, $II-NO_2$, $II-CF_3$, 및 Il-CN은 액정이 아니었다.

Effects of the pro-inflammatory milieu on the dedifferentiation of cultured fibroblast-like synoviocytes

CHOI, HONG SEO,RYU, CHUN JEIH,CHOI, HYUN MI,PARK, JIN SUNG,LEE, JAE-HOON,KIM, KANG IL,YANG, HYUNG-IN,YOO, MYUNG CHUL,KIM, KYOUNG SOO D.A. Spandidos 2012 MOLECULAR MEDICINE REPORTS Vol.5 No.4

<P>The aim of this study was to determine whether the inflammatory milieu and/or hypoxia induces the dedifferentiation of synovial cells into mesenchymal stem-like cells, which may contribute to the tumor-like growth of synovial cells. Expression of mesenchymal stem cell markers (CD24, CD44, CD90, CD106, CD146 and Stro-1) was compared among cultured fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), bone marrow mesenchymal stem cells (BM MSCs) and normal dermal fibroblasts. After the cells were stimulated with pro-inflammatory cytokines for 3 days under hypoxia or normoxia, the stem cell markers were analyzed by FACS. CD44 and CD90 were expressed constitutively in all four cell types. Only the BM MSCs strongly expressed CD146. The expression of stem cell markers was similar between FLSs from RA and those from OA patients. In addition, the expression levels in FLSs were similar to those in normal dermal fibroblasts. The stimulation of FLSs and dermal fibroblasts with IL-1β or a mixture of cytokines under hypoxia did not induce a marked change in the expression of stem cell markers. These results indirectly suggest that the pro-inflammatory milieu may be not sufficient to induce the dedifferentiation of FLSs in arthritic joints.</P>

Interleukin-2가 호산구 생존에 미치는 영향과 기전에 관한 연구

김효석 ( Hyo Seok Kim ),이영목 ( Young Mok Lee ),최영수 ( Young Soo Choi ),김경호 ( Kyung Ho Kim ),임건일 ( Geon Il Im ),문승혁 ( Jeong Sung Whan ),정성환 ( Moon Seung Hyug ),김현태 ( Hyeon Tae Kim ),어수택 ( Uh Soo Taek ),김용훈 대한결핵 및 호흡기학회 1996 Tuberculosis and Respiratory Diseases Vol.43 No.3

만성 신부전 환자에서 빈혈 개선에 따른 혈장 수용성 interleukin-2 수용체 농도의 변화

조영일,긴경수,최영숙 건국대학교 1996 學術誌 Vol.40 No.2

To evaluate the effect of anemia on the immune system in chronic renal failure (CRF) patients on hemodialysis (HD), we measured plasma sIL-2R levels in 10 CRF patients with anemia and 10 CRF patients without anemia on HD. In 10 CRF patients with anemia, plasma sIL-2R levels were measured also after correction by transfusion of packed RBCs or subcutaneous injection of rH-EPO. Plasma sIL-2R level was measured using h-IL-2R ELISA kit (Boehringer Manheim Biochemical, Germany) before and after correction of anemia. The results were as follows : Plasma sIL-2R level was 287.36±70.18 pmol/L in uremic patients with anemia and 211.35±49.85 pmol/L in uremic patients without anemia (p<0.05). After correction of anemia, plasma sIL-2R level was 299.55±98.85 pmol/L in "Low-Hct" group (Hct<26%) and 222.61 ±60.05 pmol/L in "High-Hct" group (Hct≥26%) (p<0.05). In anemic patients, plasma sIL-2R level before correction of anemia was 290.50±80.25 pmol/L and after correction of anemia was 243.74± 64.89 pmol/L (p<0.05). On conclusion, plasma sIL-2R level was higher in CRF patients with anemia than CRF patients without anemia. Plasma sIL-2R level in CRF patients with anemia became lowerd after correction of anemia. Key Word : Chronic renal failure, Plasma soluble IL-2 receptor, Anemia, Immune system.

박정희의 역사적 유산에 대한 미디어의 기억형성(memory-building) 방식

이완수(Wan Soo Lee),최명일(Myung-Il Choi) 사단법인 언론과 사회 2016 언론과 사회 Vol.24 No.2

이 연구는 역사적 공과(功過)를 놓고 논쟁적인 인물이 되고 있는 박정희 전 대통령에 대한 미디어의 기억방식을 실증적으로 살펴보았다. 사망 직후인 1979년 10월 27일부터 11월 5일까지 그의 죽음을 다룬 신문 부고기사에 나타난 사회적 기억을 의미 연결망 분석을 통해 체계적으로 관찰해보았다. 이와 동시에 이념적 지향점이 다른 신문들이 박정희라는 동일한 공인에 대해 역사적 기억과 기록을 어떻게 다르게 주조(鑄造)하고 있는지 비교분석을 했다. 분석 결과, 언론이 공통적으로 기억하는 상징어는 박정희는 5·16 혁명(현재 국어사전에는 5·16 군사정변), 경제개발, 농촌 근대화, 남북문제, 유신정책으로 나타났다. 한국사회 공동체가 기억하는 박정희의 모습은 군사정변과 유신이라는 부정적인 측면과 함께 경제개발, 근대화, 남북문제와 같은 긍정적인 측면이 중첩되어 있음을 보여준다. 그러나 신문의 이념차이에 따라 기억의 차이를 보였다. 당시 중립적인 입장을 보였던 ≪조선일보≫는 경제개발 노력과 함께 외교 강화, 그리고 개인적 추진력에 의미를 부여하는 기억구조를 보였다. 비판적 입장을 보였던 ≪동아일보≫는 경제개발 노력을 가장 중요한 의미로 강조했지만, 육사 입학, 육영수 여사, 가난한 농촌 출신과 같은 개인의 일상적 기억과 함께 극단적 권위주의라는 부정적인 기억을 드러냈다. 반면, 정부대변지였던 ≪서울신문≫은 경제개발 노력을 가장 빈번하게 강조하는 가운데 성장 위주의 정책, 일사불란한 통치스타일, 그리고 합법적 지도자 같은, 성과와 리더십을 강조하는 긍정적 의미체계를 강조했다. 박정희 죽음에 대한 공동체적 기억이 시사하는 당시의 공적 가치, 이념, 시대정신을 중심으로 토론했다. This study empirically explored media memory process on controversial issues on the former-president Park Chung-Hee. To do so, this study conducted semantic network analyses on newspaper articles regarding his death from October 27<SUP>th</SUP> 1979 to November 5<SUP>th</SUP> 1979 and compared differences on the issue by media ideology. We found that all newspapers commonly illustrated the former-president Park Chung-Hee with the symbolic words, such as 5·16 military revolution, economic development, modernizing farm villages, North Korea issues, and the Revitalizing Reforms system. Those words were also related to social memories on him that have been commonly discussed in the Korean society. The newspapers, however, had different perspectives on his performance by their media ideology. For example, The Chosun Il-bo, as a neutral stance, mainly concentrated on economic development, foreign affairs, and his personality, while Dong-a Il-bo, as a critical stance, paid attentions in reporting his achievements and authoritative activities on economic development, personal activities such as entrance of the Korean Military Academy, his wife, and his youth life. The Seoul Shinmun, as a mouthpiece of the Korean government, also emphasized his positive activities in terms of economic development and leadership style and had a similar aspects with collective memories in the Korean society.

Protective Effects of Acorn (Quercus acutissima CARR.) against IgE-mediated Allergic and Ovalbumin (OVA)-Induced Asthmatic Responses via Inhibition of Oxidative Stress

Chung, Mi-Ja,Jo, Hang-Soo,Choi, Ha-Na,Cho, Soo-Muk,Park, Yong-Il The Korean Society of Pharmaceutical Sciences and 2011 Journal of Pharmaceutical Investigation Vol.41 No.6

This work was performed to investigate the protective effect of ethanol extract (AEx) from acorn (Quercus acutissima CARR.) against allergic mediated responses in asthma model cells and mice. The AEx inhibited antigen-stimulated cytokine production such as interleukin (IL)-4, IL-13 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and AEx also inhibited intracellular reactive oxygen species (ROS) generation against IgE-mediated allergic response in rat basophilic leukaemia RBL-2H3 cells. The ovalbumin (OVA)-sensitized mice were orally administered with AEx (100 or 300 mg/kg) and authentic tannic acid (75 mg/kg) every day for 15 days. Increased TNF-${\alpha}$ production by OVA-sensitization/challenge was significantly reduced by administration of AEx. The serum triglyceride levels of asthma mice were significantly reduced after feeding for 15 days with tannic acid or AEx. The mice fed with tannic acid or AEx also exhibited a significant reduction in body weights compared to those of asthma control group. The AEx increased the heme oxygenase (HO)-1 mRNA expression in the asthma model mice and showed DPPH radical scavenging activity. These results indicate that AEx protects against IgEmediated allergic and OVA-induced asthmatic responses via direct and indirect antioxidant activities. Reduced triglyceride and body weights may provide additional protective benefits of AEx on allergic asthma.

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.