The enhanced IL-l8 production by UVB irradiation requires ROI and AP-1 signaling in human keratinocyte cell line (HaCaT)

Cho, Daeho,Kang, Jae Seung,Park, Jong Hoon,Kim, Young-In,Hahm, Eunsil,Lee, Junechul,Yang, Yoolhee,Jeon, Junho,Song, HyunKeun,Park, Hyunjeong,Kim, Taesung,Pang, Saic,Kim, Chul-Woo,Hwang, Young Il,Lee, 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Based on our recent observation that enhanced IL-18 expression positively correlates with malignant skin tumors, such as SCC and melanoma, we examined the possible role of UVB, known to be associated with skin cancer development, in the enhancement of IL-18 production using primary human epidermal keratinocytes and human cell line HaCaT. After cells were exposed to UVB irradiation in vitro, IL-18 production was examined by Northern blot analysis and ELISA, and it was found that IL-18 production is enhanced by UVB irradiation in a dose- and time-dependent manner. In addition, we confirmed that it is functionally active form of IL-18 using the inhibitor of caspase-1. The effect of UVB irradiation was blocked by antioxidant, N-acetyl-ι-cysteine (NAC), which suggested the involvement of reactive oxygen intermediates (ROI) in the signal transduction of UVB irradiation-enhanced IL-18 synthesis. We also found that UVB irradiation increased AP-1 binding activity by using EMSA with AP-1-specific oligonucleotide. Furthermore, inhibitors of UVB-induced AP-1 activity, such as PD98059, blocked enhanced IL-18 production, indicating that AP-1 activation is required for UVB-induced IL-18 production. Taken together, our results suggest that UVB irradiation-enhanced IL-18 production is selectively mediated through the generation of ROI and the activation of AP-1.

Effect of high-mobility group box 1 on keratinocytes and fibroblasts

( Chan-yang Lee ),( In-hye Kang ),( Seung-min Oh ),( Jin-woo Lee ),( Young Il Kim ),( Ki-heon Jeong ) 대한피부과학회 2020 대한피부과학회 학술발표대회집 Vol.72 No.1

Background: High-mobility group protein B1 (HMGB1) is a physiological activator of immune responses. In patients with chronic inflammatory skin disorders including lupus, atopic dermatitis, and psoriasis, HMGB1 is increased in the cutaneous lesions. Objectives: This study was designed to investigate the effect of HMGB1 on keratinocytes and fibroblasts. Methods: In this study, keratinocytes and fibroblasts were exposed to narrow band ultraviolet B (NBUVB). Thereafter, release of HMGB1 were measured. Then keratinocytes and fibroblasts were treated with recombinant HMGB1 (rHMGB1) and production of inflammatory factors such as interleukin (IL)-1β, IL-6, IL-8, IL-18, chemokine (C-X-C motif) ligand (CXCL)1, CXCL2 and tumor necrosis factor (TNF)-α were examined. Results: 24h after NBUVB irradiation, the level of HMGB1 mRNA was increased in the fibroblasts but it was decreased in the keratinocytes. Extracellular level of HMGB1 was significantly increased in both keratinocytes and fibroblasts, 72h after NBUVB irradiation. After rHMGB1 treatment, proinflammatory molecule such as CXCL-1, IL-6, IL-8 and IL-18 were significantly increased in the keratinocytes and CXCL-1, IL-6 and IL-8 were significantly increased in the fibroblasts. Conclusion: HMGB1 can be released from keratinocytes and fibroblasts by external stress such as NBUVB irradiation and leads to activation of inflammatory signaling pathways in the keratinocytes and fibroblasts.

Chronic alcohol consumption induces migration of IL-1R2+ monocytes from the bone marrow into the liver by neuro-immunologic pathway

Young-Ri Shim,Hee-Hoon Kim,Keungmo Yang,Tom Ryu,Kyurae Kim,Sung Eun Choi,Minjeong Kim,Chae-Rin Woo,Young-Sun Lee,Won-Il Jeong 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Liver is challenged by diverse detrimental substances through multiple metabolic processes, but it is less prone to inflammation. In chronic alcohol consumption, although the migration of monocytes from bone marrow (BM) into liver is increased, alcoholic hepatitis rarely occurs. Thus, we investigated the sub-population of liver macrophages showing anti-inflammatory roles through single-cell RNA sequencing (scRNA-Seq) after chronic EtOH-feeding. Interestingly, in scRNA-seq and flow cytometry analyses of hepatic macrophages, the phenotype of Ly6Clow (anti-inflammatory) cells was dramatically altered by ethanol intake. In particular, they were highly expressed interleukin-1 type II receptor (IL-1R2), a decoy receptor of IL-1β. Intriguingly, IL-1R2+ Ly6Clow macrophages showed decreased CX3CR1 expression, which was confirmed not only in the liver, but also BM and blood, suggesting monocytes from BM affected by ethanol might migrate into the liver. We found that the Leptin Receptor+ mesenchymal stromal cells (LepR+ MSCs), which were located around blood vessels expressing CX3CL1 to hold CX3CR1+ macrophages, could express alcohol dehydrogenase to metabolize ethanol in BM. Ethanol metabolism in LepR+ MSCs was induced both production of chemokines (CXCL9 and 10) and the excretion of glutamate via cystine-glutamate anti-porter xCT to recruit and activate the CXCR3+ BM NK cells to produce interferon-γ in a metabotropic glutamate receptor 5 (mGluR5)-dependent manner. Indeed, IFN-γ production was significantly decreased in EtOH-fed mice when we depleted mGluR5 in NK cells. In turn, NK cell-derived IFN-γ down-regulated CX3CR1 expression in BM Ly6Clow monocytes, consequently induced egress of Ly6Clow monocytes into the blood and migration into the liver to suppress alcoholic inflammation. In conclusion, glutamate of LepR+ MSCs imposed egress license on anti-inflammatory IL-1R2+ Ly6Clow monocytes through NK cell-derived IFN-γ-mediated suppression of CX3CR1, suggesting a potential therapeutic inter-organ crosstalk between BM and liver in alcoholic liver disease.

미슬토 추출물(Mistletoe Extract)이 위암환자의 수술 후 면역기능에 미치는 효과

양성우,신동규,김일명,윤성민,이용직,허수학,김태희,Yang, Sung-Woo,Shin, Dong-Gue,Kim, Il-Myung,Yoon, Seong-Min,Lee, Yong-Jik,Heo, Su-Hak,Kim, Tae-Hee 대한위암학회 2007 대한위암학회지 Vol.7 No.3

목적: 미슬토 추출물은 서양에서 오래전부터 사용되어진 면역치료 물질로 위암에 대해서는 연구가 부족한 실정이다. 본 연구에서 수술 받은 위암환자를 대상으로 항암제와 미슬토 추출물의 병합투여가 면역기능에 미치는 효과를 파악하기 위해 시행되었다. 대상 및 방법: 원발성 위암으로 진단받고 근치적 수술을 받은 10명의 환자를 선정하여 항암화학요법과 병행하여 수술 후 7일째부터 미슬토 추출물(ABNOVA viscum-Q)을 주 3회, 총 16주간 피하주사 하였다. 면역기능에 미치는 효과는 환자의 말초혈액에서 백혈구수와 그 분획, 백혈구에 대한 총림프구의 분율 그리고 시토카인들(Interleukin-$1{\beta}$, Interleukin-2, Interleukin-6, Interferon-$\gamma$, Tumor necrosis factor-$\alpha$)의 변화를 분석하였다. 상기 항목들은 수술 전과 수술 후 8주, 16주 총 3회 측정되었다. 결과: 남녀비는 9 : 1이며, 평균연령은 55.9세(range $33{\sim}74$세)였다. 병기는 stage Ib가 4명, II가 6명이었다. 백혈구수와 총호중구수는 기저치에 비해 치료 후 8주와 16주에 유의한 감소를 보였다. 총호산구수는 기저치에 비해 8주와 16주에 증가하는 경향을 보였지만 통계적 유의성은 없었다(P=0.15). 총림프구의 수치는 치료 전후 유의한 감소를 보이지만 백혈구 수에 대한 총 림프구의 분율은 유의하지는 않지만(P=0.91) 오히려 증가하고 있다. 각각의 시토카인들은 치료전후 큰 변화를 보이지 않았다. 결론: 치료 전후 의미있는 면역반응의 증가는 관찰하기 어려웠다. 이것은 미슬토 추출물과 항암제의 병용투여에 의한 면역활성과 억제의 상쇄반응으로 생각된다. 총호산구수가 증가하였고, 백혈구에 대한 림프구의 분율이 감소하지 않고 증가하는 양상을 보인 것은 미슬토 추출물에 의해 유발된 면역반응으로 생각된다. Purpose: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. Materials and Methods: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum $Q^{(R)}$ was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-$1{\beta}$, IL-2, IL-6, IFN-$\gamma$, TNF-$\alpha$) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. Results: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. Conclusion: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.

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.

초·중·고 학생들의 과학 탐구 능력 추이 분석을 위한 종단적 연구

우종옥,김범기,허명,김찬종,양일호,최관순,김태선 한국교원대학교 과학교육연구소 1999 청람과학교육연구논총 Vol.9 No.1

본 연구에서는 우리 나라 초·중·고등학교 학생들의 과학 탐구 능력에 대한 종단적 추이를 분석하였다. 1997년에는 우종옥 등(1998)이 개발한 검사지를 사용하였으며, 1999년에는 이를 일부만 수정하여 사용하였다. 조사 대상은 성별, 지역별 등을 고려하여 표집하였다. 조사된 자료는 각각 횡단적으로 분석하고, 이를 바탕으로 학생들의 과학 탐구능력이 어떻게 변해 가는지 종단적 추이를 분석하였다. 조사 결과 초등학생들의 과학 탐구 능력은 유의미한차이가 없었으나, 중·고등학생들의 과학 탐구 능력은 유의미하게 향상된 것으로 나타났다. 학교 과학 교육의 질을 과학적으로 관리하기 위해서는 교육과정이 추구하는 교육 목표의 달성이 성공적으로 이루어지고 있는지를 국가수준에서 주기적으로 측정하여 부진의 원인을 진단하고, 개선 방안을 계속 연구하여야 할 것이다. The longitudinal trend of elementary and secondary students' science process skills were investigated to monitor the progress of science learning. Science process skill test, developedin an earlier study on developing a national science process skills assessment system, was revised and administered for the study on March, 1999. Subjects were sampled nation wide according to sex and region. The results of this assessments were compared to those administered on February, 1997. The results showed little difference on science process skills among elementary school students. However, secondary students showed marked increase in science process skills. More systematic and long-term research for assessing science process skills should be planned and performed periodically to provide empirical and foundational data for educational policy making.

高靭性 纖維補强 시멘트 複合體를 使用한 耐震要素의 履歷特性

양일승,윤현도,김선우,박완신,한병찬,문연준 대한건축학회 2005 大韓建築學會論文集 : 構造系 Vol.21 No.1

Concrete is one of the principal materials for the structures and It is widely used all over the world While advanced technologies of concrete have been recently focused especially on developing high performance concrete In which possess high compressive strength and durability, such concrete shows extremely brittle failure under shear and tension To Improve such a poor properties, high performance fiber reinforced cement composites(HPFRCC) has been developed For forming multicrack, a large number of fiber and/or the high specific area with thinner fibers are required However, It causes difficulties for the extrusion because of the poor workability So, this theses was suggested adequate mixing method and mix proportion for cach fibers and experimentally observed Structural performance of the seismic devices made by steel bar and HPFRCC These dampers will be applied for reducing damage as weil as seismic response The advantages of the HPFRCC damper is selective structural performance, strength, stiffness, and ductility by changing configuration, bar arrangements and type of materials used The experimental results indicate that elemental ductility is much increased with decreasing damage when the HPFRCC are applied to the damper It means cementitious seismic damper for structure control is available, which has much merit in performance and cost

췌십이지장절제술 후 발생한 지속적인 구토증과 Wernicke 뇌병증

박우영,김성완,이삼연,신일선,김재민,박기형,양수진,윤진상 大韓神經精神醫學會 2007 신경정신의학 Vol.46 No.3

Wernicke encephalopathy is an acute neurologic disorder attributable to thiamine (vitamin B1) deficiency. We report the case of a 61-year-old female patient who presented Wernicke encephalopathy after surgery for pancreatic head cancer. From the ninth postoperative day, she had suffered from nausea and vomiting and had difficulties ingesting food, she was given total parenteral nutrition (TPN), but lacked adequate vitamin (thiamine) supplementation. After 28 days, she developed ataxia, ophthalmoplegia, and mental confusion. The magnetic resonance image showed pathologic changes in the medial thalamus,periaqueductal gray matter, medulla and mamillary bodies. The blood level of thiamine was very low. After intravenous and oral supplementation of thiamine (200 mg/day), consciousness was soon normalized and neurologic symptoms have gradually been improving. Nausea and vomiting disappeared after administration of a low dose of mirtazapine (7.5 mg/day). We emphasize the importance of thiamine supplementation to the patients who suffer from vomiting which hinders them from taking food and who require prolonged TPN.

심실중격결손증-치험 1예-

조광현,우종수,황윤호,이양행,박철호,김종성,김철호,이경순,조영일,박태인 인제대학교 1985 仁濟醫學 Vol.6 No.4

A successful treatment of infants and children with congenital heart defects depends upon several factors: diagnosis must be accurate, the operative technique, including techniques of perfusion and myocardial preservation, must be suited to the needs of patients and intensive cares, including accurate anesthesia, must be applied through all stages of investigation and treatment, i.e. before, during and after the operation. Recently we performed a open heart surgery successfully for a six-years old girl who had suffered from frequent upper respiratory tract infection and mild to moderate exertional dyspnea with congenital heart defects (ventricular septal defect, Kirklin type II, with patent foramen ovale). The operation and postoperative course were very smooth. And now we report this with review of literatures.

예비 과학교사들의 가설 창안 과정에 대한 탐색적 분석

권용주,양일호,정원우 한국교원대학교 과학교육연구소 2000 청람과학교육연구논총 Vol.10 No.1

본 연구에서는 먼저 생물학 관련 내용인 생선같은 어류와 소고기나 돼지고기같은 육상동물 근육의 조직이 서로 차이가 나는 현상에 대한 원인적 가설을 창안하는 기능을 검사하는 도구를 개발하여, 예비 과학교사 23명에게 투입하였다. 그런 다음, 피험자들이 창안한 가설을 정상적 분석 방법으로 분석하여 공통점과 차이점을 분석한 뒤, 가설 및 가설창안과정에서 발견되어지는 경향성(들)을 분석하고자 하였다. 피험자들이 창안한 가설은 모두 총 52개였는데, 본 연구에서 이들을 내용적 속성 측면에서 분석해 본 결과 이들 가설은 크게 조작적 가설 또는 이론적 가설로 분류되었다. 이들이 창안ㄴ한 52개의 가설 가운데 조작적 가설은 45개였고, 나머지 7개는 이론적 가설에 해당되었다. 또한 학생들의 가설창안 과정을 분석해 본 결과, 가설을 창안과정에 사용된 경험적 지식과 새로운 미지의 상황 사이의 유사성 정도에 근거한 외전의 논리적 추론을 중심으로 분석했을 때 4단계로 분류되었다. 특히 피험자들의 가설창안과정의 분석 결과는 약 80%이상이 가설을 창안할 때 기지의 경험적 지식과 미지의 현재 상황과의 유사성 정도를 논리적으로 추론하는 것이 부적절한 모습을 나타내었다. Hypothesis is defined as a single proposition proposed as a possible explanation for the occurrence of some observed phenomena. The purpose of this study was to analyze and categorize hypotheses generated by students on the cause of difference between the structures of muscles of the fishes and the terrestrial animals. A hypothesis-generating test was administered to 23 three college students who were majoring in science education. The study showed that college students generated manipulative and theoretical hypotheses as proposed explanations for the structural difference between muscles of the fishes and the terrestrial animals. Furthermore, students generated several hypotheses which were categorized by the quality of abductive process based on the degree of likeness between experienced knowledge and current phenomena. This study also discusses the implications of these findings for teaching and research in science education.