• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.161-171
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• 1999

Background: Interleukin-12 (IL-12) can induce antitumor effects in vivo. This antitumor effect is associated with T cell infiltration but the effect of IL-12 on the steps of T cell migration into the tumor tissue has not been fully elucidated. This study focused on the effect of IL-12 on the tumor growth and the metastasis and on the expression of E-selectin, an adhesion molecule which is activated endothelial specific in its expression. In addition, we studied whether the expression of E-selectin is associated with the TNF-$\alpha$, a cytokine that its production is increased by IL-12 and has functions inducing a variety of adhesion molecules. Methods: Mice of C57BL/6 strain were injected with Lewis lung cancer cells followed by either IL-12, TNF-$\alpha$, or normal saline by intraperitoneal route. Twenty eight days after tumor cell inoculation, metastatic nodules of lung were enumerated and immunohistochemical staining of the subcutaneous tumors were performed with monoclonal antibodies to CD4, CD8, CD16, and E-selectin. In IL-12 treated mice, the subcutaneously implanted Lewis lung tumors were decreased in size and the metastases were also decreased in number compared to control mice. On tumor tissues, increased infiltration of CD4+, CD8+, and CD16+ cells were oberved in IL-12 treated mice compared to control mice. In control mice, E-selectin was absent on tumor vessels, but the expression of E-selectin was increased on tumor vessels of IL-12 treated mice. Administration of TNF-$\alpha$ increased not only the expression of E-selectin but also infiltrations of CD4+, CD8+, and CD16+ cells on tumor tissues. Conclusions: These results demonstrate that IL-12 inhibits tumor growth and metastases through infiltrations of inflammatory cells in mouse model of Lewis lung carcinoma and E-selectin may playa role in inflammatory cell recruitment on tumor tissue following IL-12 administration. Also, TNF-$\alpha$ may have a role as a mediator responsible for the IL-12 induced expression of E-selectin.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.936-944
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• 1996

Background: Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. Adhesion molecules and gene transcription of the inflammatory mediators are known to be associated in this process. To evaluate whether adhesion molecule and transcriptional activation of the inflammatory substances are also involved in the activation of human alveolar macrophage by the adherence procedure, we designed this experiment. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be nonnal by chest cr and alveolar macrophage was harvested. To measure the expression of Interleukin-8(IL-8) mRNA, manganese superoxide dismutase(SOD) mRNA and CD11/CD18 mRNA in human alveolar macrophage of both adherence state and suspension state, Northern blot analysis was done at 0, 2, 4, 8 and 24hrs after the adherence to plastic surface and during suspension state. Then, phorbol myristate acetate(pMA) and N-formyl-methionyl-leucyl-phenylalanine(fMLP) were added respectively in the same experimental condition. Result : 1) Human alveolar macrophages in the adherent state induced IL-8 mRNA and SOD mRNA expression which was maximal at 8 hours after the adherence to plastic surface. But we could not observe the upregulation of CD18 mRNA by surface adherence. 2) PMA induced these mRNA expression both in the adherent cell and the nonadherem cells, but the induction of mRNA expression by fMLP occurred only in the adherent cells. Conclusion: These results suggest that adherence of huamn alveolar macropahge is an important cell-activating event that may play a critical role in the modulation of lung inflammatory respones.

• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

• Journal of Conservation Science
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• v.32 no.2
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• pp.167-178
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• 2016

Despite the size layer is an important part for conserving the artworks in the configuration of oil painting, the conservation scientific approaches of that have not been made yet. Therefore, this study produced standard samples on the basis of the analysis results of oil painting works, and carried out the evaluation of functions of the size layer materials. As a result of literature material, traditionally, animal glue was used for the size layer, whereas synthetic resin have been used in combination with animal glue since the modern age, in particular, it was identified that Polyvinyl Acetate(PVAc) was in general use. As a result of analysis of oil painting works, size layer was detected on the support and it was identified as animal glue. As a result of analysis based on Funaoka canvas for ground, it showed that the lead oxide and the titanium dioxide were the main constituents. On the basis of these results, standard samples were produced. As a result of evaluation on the functions of the size layer materials, in the case of the animal glue, stable result was observed in the shrinkag expansion rate, whereas slight weakness was observed in moisture proofing, color, and tensile strength, and dense cracks were found on surface. As for PVAc(A), moisture proofing, color, and the tensile strength exhibited stable results. Higher shrinkage rate was observed and the cracks with wide gaps were found on surface. As for PVAc(B), tensile strength, shrinkage expansion rate, and surface observation showed stable results, whereas moisture proofing property showed poor results. Different aspects were observed in each experiment, and this phenomena were considered to be due to the density and the adhesion properties between the hydrophilic and hydrophobic molecules in the size layer materials. The results are expected to be used as materials for the oil painting work conservation henceforth.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.462-474
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• 1994

Background : In acute lung injury, activated neutrophils play an important role in tissue damage. For neutrophils to participate in lung inflammation, chemotactic factors released from mononuclear phagocytes are needed to bring these cells to the local site of inflammation, with interleukin-8 (IL-8) being one of the most specific and important chemotactic factors for neutrophils. IL-8 also induces the expression of adhesion molecules and activates neutrophils to release various inflammatory mediators. Lipopolysaccharide(LPS) is one of the most important causes of adult respiratory distress syndrome and can cause release of many inflammatory cytokines including IL-8 leading to acute lung injury. But little is known about the regulatory mechanism of LPS-induced IL-8 gene expression in mononuclear phagocytes. Method : Human alveolar macrophages(HAM) and peripleral blood monocytes(PBMC) were isolated from healthy volunteers. Time and dose relationship of LPS-induced IL-8 mRNA expression was observed by Northern blot analysis. To evaluate the regulatory mechanism of LPS-induced IL-8 gene expression, pretreatment of actinomycin D(AD, $5{\mu}g/ml$) and cycloheximide(CHX, $5{\mu}g/ml$) was done and Northern blot analysis for IL-8 mRNA and ELISA for immunoreactive IL-8 protein in culture supernatant were performed. Results : 1) In HAM, dose and time dependent LPS-induced IL-8 mRNA expression was observed with peak mRNA level at 8 hours post-stimulation. 2) In PBMC, dose and time dependent LPS-induced IL-8 mRNA expression was also observed with peak mRNA level at 4 hours post-stimulation. 3) AD decreased expression of LPS-induced IL-8 gene expression at both mRNAand protein levels in both types of cells. 4) CHX decreased expression of LPS-induced IL-8 gene expression at protein level in both cell types but in HAM, superinduction of IL-8 mRNA was observed while decreased expression of IL-8 mRNA was observed in PBMC. Conclusion : Time and dose dependent LPS-induced IL-8 gene expression was observed in mononuclear phagocytes which is at least partly regulated pretranslationally. LPS-induced IL-8 mRNA expression in HAM needs no de novo protein synthesis and may be under the control of a labile repressor protein while de novo protein synthesis may be needed in PBMC.

• Molecules and Cells
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• v.38 no.3
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• pp.210-220
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• 2015

Athletic performance is an important criteria used for the selection of superior horses. However, little is known about exercise-related epigenetic processes in the horse. DNA methylation is a key mechanism for regulating gene expression in response to environmental changes. We carried out comparative genomic analysis of genome-wide DNA methylation profiles in the blood samples of two different thoroughbred horses before and after exercise by methylated-DNA immunoprecipitation sequencing (MeDIP-Seq). Differentially methylated regions (DMRs) in the pre-and post-exercise blood samples of superior and inferior horses were identified. Exercise altered the methylation patterns. After 30 min of exercise, 596 genes were hypomethy-lated and 715 genes were hypermethylated in the superior horse, whereas in the inferior horse, 868 genes were hypomethylated and 794 genes were hypermethylated. These genes were analyzed based on gene ontology (GO) annotations and the exercise-related pathway patterns in the two horses were compared. After exercise, gene regions related to cell division and adhesion were hypermethylated in the superior horse, whereas regions related to cell signaling and transport were hypermethylated in the inferior horse. Analysis of the distribution of methylated CpG islands confirmed the hypomethylation in the gene-body methylation regions after exercise. The methylation patterns of transposable elements also changed after exercise. Long interspersed nuclear elements (LINEs) showed abundance of DMRs. Collectively, our results serve as a basis to study exercise-based reprogramming of epigenetic traits.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.55-66
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• 1998

Pathophysiological mechanism of hemorrhagic fever with renal syndrome (HFRS) is not fully understood. Major clinical findings of HFRS patients are widespread hemorrhage, acute renal failure and shock. Basic lesion is vascular injury with microvascular hemorrhage and relatively little inflammation. According to autopsy findings, renal medulla shows focal hemorrhage, tubular necrosis and interstitial mononuclear infiltrates. The predominant cell type in the renal and pulmonary interstitium is a fibroblast and it participates in the healing process at the injury site by secreting a large amount of extracellular matrix proteins. Cultured human lung fibroblasts and Mongolian gerbil fibroblasts were known to be good host cells for the hantaan virus. It is possible that not only the endothelial cell but also the fibroblast is a target of Hantaan virus and the fibroblast might be involved in the pathogenesis and the healing process in HFRS. Integrins are adhesion molecules, and act as receptors for many extracellular matrix proteins. Recently, there are many reports that cell surface integrins influence on some viral infections or reversely viruses influence on the expression of integrins. The ${\alpha}_5{\beta}_1$ integrin is a major receptor for the fibronectin which is an important extracellular matrix protein secreted by fibroblasts. In this study, the role of ${\alpha}_5{\beta}_1$ integrin in the infection of Hantaan virus was examined by using anti-${\alpha}_5{\beta}_1$, integrin, anti-${\alpha}_5$ integrin and anti-${\beta}_1$, integrin antibodies in chicken embryo fibroblasts (CEF) and Mongolian gerbil fibroblasts(MGF). The treatment of anti-${\alpha}_5{\beta}_1$, integrin antibody in CEF reduced the virion titers 26.8% and the amount of nucleocapsid N protein 32.6% when compared with control CEF. When MGF were treated with anti-${\alpha}_5$, anti-${\beta}_1$ and anti-${\alpha}_5{\beta}_1$ integrin antibodies, virion titers were reduced by 26.5%, 29.4% and 28.7% and the amount of nucleocapsid N protein were reduced by 65.2%, 59.7% and 72.6%. These results suggested that ${\alpha}_5{\beta}_1$ integrin might act as a receptor for the Hantaan virus or blocking of ${\alpha}_5{\beta}_1$ integrin influences on the viral replication in CEF and MGF. It is also possible that the blocking of only one subunit of integrin represents similar results in that of whole molecule.

• Development and Reproduction
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• v.13 no.1
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• pp.1-11
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• 2009

Implantation itself is governed by an array of endocrine, paracrine and autocrine modulators, of embryonic and maternal origin. Window of implantation is the unique temporal and spatial expression of factors allows the embryo to implant via signaling, appositioning, attachment, and invasion in a specific time frame of $2{\sim}4$ days. When the embryo has arrived in the uterine cavity, a preprogrammed sequence of events occurs, which involves the production and secretion of a multitude of biochemical factors such as cytokines, growth factors, and adhesion molecules by the endometrium and the embryo, thus leading to the formation of a receptive endometrium. Cytokines such as LIF, CSF-1, and IL-1 have all been shown to play important roles in the cascade of events that leads to implantation. Integrin, L-selectin ligands, glycodelin, mucin-1, HB-EGF and pinopodes are involved in appositioning and attachment. The embryo also produces cytokines and growth factors (ILs, VEGF) and receptors for endometrial signals such as LIF, CSF-1, IGF and HB-EGF. The immune system and angiogenesis play an important role. The usefulness of these factors to assess endometrial receptivity and to estimate the prognosis for pregnancy in natural and artificial cycles remains to be proven. Integrins, pinopodes, glycodelin and LIF (from biopsies) are promising candidates; from uterine flushings, glycodelin and LIF are also candidates. The ideal serum marker is not available, but VEGF, glycodelin and CSF have some clinical implications. Further evaluation that includes larger groups of infertile women and fertile controls are needed to elucidate whether their presence in plasma, flushing fluid, or endometrial samples can be used as some kind of a screening tool to assess endometrial function and prognosis for pregnancy before and after artificial reproductive therapy. A better understanding of their function in human implantation may lead to therapeutic intervention, thereby improving the success rate in reproduction treatment. New molecular techniques are becoming available for measuring both embryonic and endometrial changes prior to and during implantation. The use of predictive sets of markers may prove to be more reliable than a single marker. Ultimately, the aim is to use these tools to increase implantation in artificial cycles and consequently improve live-birth rates.

• Tuberculosis and Respiratory Diseases
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• v.45 no.3
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• pp.553-564
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• 1998

Background: The immediate hoot response to LPS is the production of proinflammatory cytokines that act as intercellular mediators in inflammatory reactions, including acute lung injury. These "early response" cytokines transmit signals from recognition cells to target or effector cells. This host response is further amplified by the expression of leukocyte chemoattractants, growth factors, and adhesion molecules, resulting in an array of proinflammatory events. This experiment was performed to define the lung origin of proinflammatory cytokines, such as TNF-$\alpha$, IL 6 in early periods of endotoxin induced acute lung injury (ALI). Method: The healthy male Sprague-Dawley, weighted 150 - 250g, were divided into saline control (NC) and endotoxemia-induced ALI (ETX-), and leukopenic endotoxemia-induced ALI (CPA-ETX-Group) which was induced by cyclophosphamide, 70 mg/kg i.p. injection. Acute lung injury was evoked by LPS, 5 mg/kg, intravenously administered. Bronchoalveolar lavage was performed at 0, 3, 6 h after LPS-treated to estimate the influx of phagocytes and concentration of total protein, and cytokines as TNF-$\alpha$ and IL 6 by a bioassy using MIT method. We also examined the localization of TNF-$\alpha$ and IL 6 protein in endotoxemia-challenged lung tissue by immunohistochemical stain (IH). Results: The total cell, macrophage and PMN count in BALF were elavated in ETX group compared to NC(p<0.05). In CPA-ETX group, total cell and macrophage count in BALF were not changed compared to NC. but PMN count was markedly reduced and it took part in less than 0.1 % of total BAL cells (p<0.01). The protein concentration in BALF were significantly increased in ETX and CPA-ETX group Compared to NC (p<0.05), but there was significant difference between ETX- and CPA-ETX group only at 6 h (p<0.05). This observation suggested that even if PMNs are involved in the pathogenesis of acute lung injury, their role cannot be viewed as essential The concentration of TNF-$\alpha$ and IL 6 in BALF was significantly increased in the ETX- and CPA-ETX group compared to NC. There was no difference between ETX- and CPA-ETX group. In IH, anti-TNF-$\alpha$- and anti-IL 6 antibody was strongly localized at interstitial monocytes and alveolar macrophages in endotoxemia-challenged lung tissue. From above point of view, activated alveolar macrophage/monocyte considered as a prominent source of proinflammatory cytokines in endotoxemia-challenged lung injury. Conclusion: The prominent source of proinflammatory cytokines in early periods of endotoxemia-induced lung injury will be the activated resident macrophages like an alveolar macrophage and interstitial monocytes. The pulmonary macrophage/monocyte will impact the initiation and continuance of lung injury without PMNs's certain inflammatory role, particularly in endotoxemia-induced acute lung injury.