Use of genomic techniques to screen for potential immunotoxic effects

( Kyung Hee Sohn ),( In Young Kim ),( Juno H. Eom ),( Jong Kwon Lee ),( Jin Ho Kim ),( Jung Hun Ju ),( Hwa Chul Jung ),( Ji Hye Lee ),( Moon Sung Choi ),( Hyung Soo Kim ),( Seung Hee Kim ),( Kui Lea P 한국동물실험대체법학회 2007 한국동물실험대체법학회 학술대회집 Vol.2007 No.1

Application of genomic data to elucidate or predict an organism`s response to a toxicant is referred to as toxicogenomics. Toxicogenomics is increasingly applied to study alterations in gene expression after immunotoxicant exposure, but published data are still limited. The present study was performed to explore the potential role of genomics techniques for immunotoxicity screening. Genomic data alone are, however, insufficient to screen chemicals for immunotoxic potentialand should be anchored to a phenotypic marker. Therefore, we performed both DNA microarray analysis and traditional immunotoxicity tests to clarify the connection between changes in gene expression and pathological/functional endpoints. Cyclosporin A(CsA), tacrolimus(FK506), hexachlorobenzene(HCB) were used as immunotoxicants. Immunological effects of these chemicals on Balb/c mouse were confirmed by changes in parameters related to pathology, hematology, innate immunity, humoral immunity and cellular immunity. On the other hand, total RNAs were prepared from spleens and thymuses of Balb/c mice which were orally dosed with each chemical for 28 days. The changes in gene expression levels were analyzed using Applied Biosystems Mouse Genome Survey Microarray. Differentially expressed genes(DEG) were selected and classified through related biological processes and signal pathways. Comparative toxicogenomic analysis from these differential gene expression profiles was performed. Ultimately, the use of genomics techniques as a potential screening tools for immunotoxicity and as a technique to identify mode or mechanism of action will be discussed.

Structure-activity relationship evaluation of isoflavonoid on IL-5 mediated proliferation of Y16 cells

( Jung Hun Ju ),( Young Soo Kim ),( Kyung Rak Min ),( Jong Kwon Lee ),( Seung Hee Kim ),( Kui Lea Park ) 한국동물실험대체법학회 2007 한국동물실험대체법학회 학술대회집 Vol.2007 No.1

Interleukin (IL)-5 is mainly produced from Th2 cells activated by allergen. The cytokine acts preferentially on eosinophils. IL-5 promotes growth and differentiation of eosinophils from their progenitor cells, and activates the cells to release chemical mediators for the inflammatory response. Sophoricoside, a natural isoflavone glycoside from S. japonica, showed an IC50 value of 11.3 uM on IL-5 mediated proliferation of Y16 cells. To develop novel IL-5 inhibitor with sophoricoside as a lead compound, 100 kinds of synthetic isoflavone analogs have been prepared. Among them, synthetic isoflavone(7-cyclohexylmethoxy-3-(4-hydroxyphenyl) chromen-4-one) substituted with cyclohexylmethyl group showed an IC50 value of 5.2 uM on the IL-5 bioassay. Pharmacophore of the isoflavone analogs to inhibit IL-5 bioactivity seems to require of isoflavone 1) introduction of cyclohexylmethoxy group at 5 or 7 position of A ring of isoflavone, which may act as a bulky group for interacting with hydrophobic pocket in putative target, 2) existence of phenolic hydroxy group at 4` position of B ring, and 3) planarity between A and C rings. Furthermore, 7-cyclohexylmethoxy-3-(4-hydroxyphenyl) chromen-4-one compound inhibited IL-3 or GM-CSF mediated proliferations of Y16 cells with IC50 values of 6.8 uM or 5.9 uM, respectively. As the mechanism of action, 7-cyclohexylmethoxy-3-(4-hydroxyphenyl) chromen-4-one suppressed IL-5 induced c-mycexpression through inhibitory action on activation of JAK-2 and MAP kinases (p38 and ERK1/2). However, sophoricoside inhibited IL-5 induced phosphorylation of JAK-2 and ERK1/2 but it did not suppress p38 MAP kinase and c-myc expression.

Life Science : Inhibitory effect of 4-0-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kappaB in vitro and in vivo models

( Young Jung Lee ),( Dong Young Choi ),( Im Seop Choi ),( Ki Ho Kim ),( Young Hee Kim ),( Hwan Mook Kim ),( K Iho Lee ),( Won Gil Cho ),( Lea Kyung Jung ),( Sang Bae Han ),( Jin Yi Han ),( Sang Yoon N 영남대학교 약품개발연구소 2012 영남대학교 약품개발연구소 연구업적집 Vol.22 No.0

BACKGROUND: Neuroinflammation is important in the pathogenesis and progression of Alzheimer disease (AD). Previously, we demonstrated that lipopolysaccharide (LPS)-induced neuroinflammationcaused memory impairments. In the present study, we investigated the possible preventive effects of 4-O-methylhonokiol, a constituent of Magnolia officinalis, on memory deficiency caused by LPS, along with the underlying mechanisms. METHODS: We investigated whether 4-O-methylhonokiol (0.5 and 1 mg/kg in 0.05% ethanol) preventsmemory dysfunction and amyloidogenesis on AD model mice by intraperitoneal LPS (250 μg/kg daily 7 times) injection. In addition, LPS-treated cultured astrocytes and microglial BV-2 cells were investigated for anti-neuroinflammatory and anti-amyloidogenic effect of 4-O-methylhonkiol (0.5, 1 and 2 μM). RESULTS: Oral administration of 4-O-methylhonokiol ameliorated LPS-induced memory impairment in a dose-dependent manner. In addition, 4-O-methylhonokiol prevented the LPS-induced expression of inflammatory proteins; inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as activation of astrocytes (expression of glial fibrillary acidic protein; GFAP) in the brain. In in vitro study, we also found that 4-O-methylhonokiol suppressed the expression of iNOS and COX-2 as well as the production of reactive oxygen species, nitric oxide, prostaglandin E2, tumor necrosis factor-α, and interleukin-1β in the LPS-stimulated cultured astrocytes. 4-O-methylhonokiol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus of the brain and cultured astrocytes. Consistent with the inhibitory effecton neuroinflammation, 4-O-methylhonokiol inhibited LPS-induced Aβ1-42 generation, β- and γ-secretase activities, and expression of amyloid precursor protein (APP), BACE1 and C99 as well as activation of astrocytes and neuronal cell death in the brain, in cultured astrocytes and in microglial BV-2 cells. CONCLUSION: These results suggest that 4-O-methylhonokiol inhibits LPS-induced amyloidogenesisvia anti-inflammatory mechanisms. Thus, 4-O-methylhonokiol can be a useful agent againstneuroinflammation-associated development or the progression of AD.

중학교 운동선수의 체벌 실제와 문제점 및 개선방안

이정래(Lee Jung-Lea),송은주(Song Eun-Jo),오세경(Oh Se-Kyung),박창범(Park Chang-Beom) 한국체육과학회 2006 한국체육과학회지 Vol.15 No.3

The actual states of corporal punishments on athletes at the middle schools were seen through in this study. As problems related with them have been investigated through the deep interview that is one of the qualitative researching methods, they have been disclosed and the solutions to them have been searched. And the contents of this study are just like the following. Middle school athletes have been skeptical about their sport because of corporal punishment, and there are some reasons they are punished by their managers or coaches; an insufficiency of their training goal, a poor grade of their matches or games, a lack of their powers of concentration, and their deed breaking the rule or discipline that they must be obeyed during the life of athletes, the corporal punishment that could be raised doubts in their mind about an educational meaning and justice frequently occurs. However, middle school athletes are thought to need this corporal punishment in a certain occasions. And they feel the rejection of severe punishment to improve their game skills. Also the effect of corporal punishment does not last for a long time, they recognize to need the improvement of their game skills that has done by their will rather than corporal punishment The corporal punishment on middle school athletes results in several problems such as the nondemocratic structure of decision-making, the absence of criteria about punishment, the decreasing of interest in their sport, the extrications from their team, and the reproduction of passive human type. To improve these problem, depth research is needed to study, for example establishment of manager's instructive philosophy about normal education and the development of training program for it, the establishment of strick standard about corporal punishment and giving rewards for desirable deed and the alternative methods if instruction.

Effect of Dermatophagoides pternyssinus allergen 1 on atopic dermatitis-like lesion induced by contact allergen in hairless mice

Jong Kwon Lee,Jung Hun Ju,Jinho Kim,Jung Rae Kim,Eun Young Chun,In Young Kim,Kyung Hee Sohn,Seung Hee Kim,Kui Lea Park 한국실험동물학회 2007 한국실험동물학회 학술발표대회 논문집 Vol.2007 No.-

Polybrominated Diphenyl Ethers Orally Administration to Mice Were Tansferred to Offspring during Gestation and Lactation with Disruptions on the Immune System

Hong, Soon-Keun,Sohn, Kyung-Hee,Kim, In-Young,Lee, Jong-Kwon,Ju, Jung-Hun,Kim, Jin-Ho,Lim, Chae-Hyung,Han, Beom-Seok,Jung, Hwa-Chul,Lee, Jin-Yong,Park, Kui-Lea The Korean Association of Immunobiologists 2010 Immune Network Vol.10 No.2

Background: The present study was undertaken to examine the immunological effects of pentabrominated diphenyl ether (penta-BDE) and decabrominated diphenyl ether (deca-BDE) on the immune system of the dams and the developmental immune system of the offsprings. Methods: In this study, mated female C57BL/6J mice were orally administered penta-BDE, deca-BDE or corn oil for 5 weeks, from gestational day 6 to lactational day 21. Results: The body weight of PND21 exposed to penta-BDE was significantly decreased relative to control mice, but that of post-natal day 63 (PND63) were recovered. Orally dosed dams with penta-BDE had significantly smaller absolute and relative spleen masses than control mice. Absolute and relative spleen and thymus masses of PND21 exposed to penta-BDE were significantly decreased over control. The exposure of dams and PND21 with penta-BDE reduced the number of splenocytes and thymocytes. As results of hematologic analysis, percentage WBC and percentage neutrophils increased in dams with deca-BDE. Splenic T cell proliferation in dams and PND21 exposed to penta-BDE was increased, and there were no significant difference in splenic B cell proliferation in all treatment groups. As results of flow cytometric analysis of splenocyte, percentage total T cell, Th cell and Tc cell in PND21 exposed to penta-BDE was slightly increased, and percentage macrophage in dams and PND21 exposed to deca-BDE was decreased. The ELISA results of antibody production show no significant difference in all treatment groups relative to controls. Conclusion: These results imply that PBDEs given to the dam were transferred to the offspring during gestation and lactation, and PBDEs transferred from the dam affect immune system of offspring.

BrdU 면역조직화학염색을 이용한 국소 림프절 시험법(Local Lymph node assay) 연구

이종권 ( Jong Kwon Lee ),주정흔 ( Jung Hun Ju ),김정래 ( Jung Rae Kim ),손경희 ( Kyung Hee Sohn ),김진호 ( Jin Ho Kim ),김인영 ( In Young Kim ),전은영 ( Eun Young Jun ),김승희 ( Seung Hee Kim ),박귀례 ( Kui Lea Park ) 한국동물실험대체법학회 2007 동물실험대체법학회지 Vol.1 No.1

Allergic contact dermatitis (skin sensitization) may be caused by a wide variety of chemicals. A murine local lymph node assay(LLNA) has been developed as an alternative to guinea pig models for assessing the contact sensitization potential of chemical. This study was carried out to evaluate the skin sensitization potential for chemicals in Balb / c mice by LLNA. A murine local lymph node assay(LLNA) has been developed as an alternative to guinea pigs for contact sensitization potential. This study was carried out to investigate the skin sensitization potential of four allergenic chemicals, strong allergen, p-phenylenediamine (PPD), moderate allergen, cinnamaldehyde, and isoeugenol, and weak allergen, citral, by LLNA using a non-radioistopic endpoint. Female Balb/c mice were exposed topically to PPD, cinnamaldehyde, isoeugenol, and citral following LLNA protocol. Lymph node (LN) weight and cell proliferation in ears and auricular lymph node using bromode- oxyuridine (BrdU) immunohistochemistry were evaluated. Skin reactions, consisting of increased ear thickness and the presence of inflammatory infiltrates, were observed in mice treated with PPD, cinnamaldehyde, and isoeugenol compared to the vehicle control. The relative weight of the lymph nodes in the mice treated with four allergen were increased compared to vehicle control. The SI values in lymph nodes of the mice exposed to 10% PPD and 30% isoeugenol were increased more than threefold compared with that of the control. The SI values of the chemicals showed the comparative strength of proliferation in lymph node as following order of PPD>cinnamaldehyde>isoeugenol>citral. These results suggest that the measurement of the SI in lymph node using BrdU immunohistochemistry could provide a useful method to screen the allergenic potential of chemicals.

연구논문 : BrdU 면역조직화학염색을 이용한 국소 림프절 시험법(Local Lymph node assay) 연구

이종권 ( Jong Kwon Lee ),주정흔 ( Jung Hun Ju ),김정래 ( Jung Rae Kim ),손경희 ( Kyung Hee Sohn ),김진호 ( Jin Ho Kim ),김인영 ( In Young Kim ),전은영 ( Eun Young Jun ),김승희 ( Seung Hee Kim ),박귀례 ( Kui Lea Park ) 한국동물실험대체법학회 2007 동물실험대체법학회지 Vol.1 No.1

Allergic contact dermatitis (skin sensitization) may be caused by a wide variety of chemicals. A murine local lymph node assay(LLNA) has been developed as an alternative to guinea pig models for assessing the contact sensitization potential of chemical. This study was carried out to evaluate the skin sensitization potential for chemicals in Balb / c mice by LLNA. A murine local lymph node assay(LLNA) has been developed as an alternative to guinea pigs for contact sensitization potential. This study was carried out to investigate the skin sensitization potential of four allergenic chemicals, strong allergen, p-phenylenediamine (PPD), moderate allergen, cinnamaldehyde, and isoeugenol, and weak allergen, citral, by LLNA using a non-radioistopic endpoint. Female Balb/c mice were exposed topically to PPD, cinnamaldehyde, isoeugenol, and citral following LLNA protocol. Lymph node (LN) weight and cell proliferation in ears and auricular lymph node using bromode- oxyuridine (BrdU) immunohistochemistry were evaluated. Skin reactions, consisting of increased ear thickness and the presence of inflammatory infiltrates, were observed in mice treated with PPD, cinnamaldehyde, and isoeugenol compared to the vehicle control. The relative weight of the lymph nodes in the mice treated with four allergen were increased compared to vehicle control. The SI values in lymph nodes of the mice exposed to 10% PPD and 30% isoeugenol were increased more than threefold compared with that of the control. The SI values of the chemicals showed the comparative strength of proliferation in lymph node as following order of PPD>cinnamaldehyde>isoeugenol>citral. These results suggest that the measurement of the SI in lymph node using BrdU immunohistochemistry could provide a useful method to screen the allergenic potential of chemicals.

Evaluation of Antioxidant and Anticancer Activity of Steam Extract from The Bamboo Species

Ji Su Kim,Hyung Chul Lee,Jong Soo Jo,Ji Young Jung,Yeong Lea Ha,Jae Kyung Yang 한국목재공학회 2014 목재공학 Vol.42 No.5

Natural plant extract has been the subject of intense research aiming in elucidating the underlying mechanisms oftheir chemopreventive effects upon various forms of human cancers. The objective of our study was to evaluate thenatural antioxidants and anticancer agent potential of Phyllostachys. The chemical composition of steam extract fromPhyllostachys was carried out using GC-MS. The steam extract of Phyllostachys was dominated by monoterpenes(62.96% - 71.36%) and sesquiterpenes (23.58% - 33.13%) as the main compounds. The antioxidant activities of thesteam extract was determined using a DPPH scavenging and hydrogen peroxide scavenging activity test systems. Furthermore, the amounts of total phenolics in steam extract were determined spectrometrically The steam extract ofP. pubescens and P. bambusoides were presented the high activity (69.4% and 64.0%, respectively.). The steam extractfrom Pyllostachys species showed a hydrogen peroxide scavenging activity of approximately 50.4% - 54.6% whencompared to that of the standard gallic acid. The anticancer activities of steam extract were determined using a MTTassay. Assessment of the cytotoxic effect of the steam extract on PC-3 cells showed that the P. bambusoides (20.85%)and P. pubescens (20.41%) were superior in induced cytotoxicity compared with the steam extract of P. nigra var. henonis(1.15%). Findings from this study indicated that steam extract of P. bambusoides and P. pubescens possessedpotential as medicinal drug especially in prostate cancer treatment.

곶감 경영규모별 수익성 비교

이기우(Ki-U Lee),송인규(In-Gyu Song),김세종(Se-Jong Kim),조재욱(Jae-Wook Cho),정경미(Kyung-Mi Jung),김국래(Gook-Lea Kim) 한국원예학회 2013 한국원예학회 학술발표요지 Vol.2013 No.10