• BMB Reports
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• v.35 no.5
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• pp.482-487
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• 2002

Early activation of human peripheral blood polymorphonuclear neutrophils is characterized by their morphological changes from spherical to polarized shapes. The endotoxins from enteric pathogens (S. dysenteriae type 1, V. cholerae Inaba 569B, S. typhimurium, and K. pneumoniae) were assessed by their ability to induce morphological polarization of the neutrophils as measures of early activation. Phagocytic activity, adhesion, chemokinetic locomotion, and nitroblue tetrazolium (NBT) dye-reduction ability measured the later activation of the cells. Neutrophils showed distinct morphological polarization in suspension over a wide range of concentrations of these endotoxins when were compared with those that were induced by the standard chemotactic factor, N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP). It was discovered that all of the endotoxins induced locomotor responses in neutrophils in suspension that were dose- and time-dependent. The optimum concentration for the endotoxins of S. dysenteriae, V. cholerae, and K. pneumoniae was 1 mg/ml in which 71, 69, and 66% of the neutrophils were polarized. However, the S. typhimurium dose was 2 mg/ml in which 50% of the cells responded. Neutrophils that were stimulated with endotoxins also showed increased random locomotion (p<0.005) through cellulose nitrate filters, but an enhanced adhesion of the cells to glass surfaces (p<0.03). These are important functions of these cells to reach and phagocytose damaged cells, as well as invading microorganisms. Interestingly, the endotoxins had a highly-significant inhibitory effect upon the proportions of neutrophils phagocytosing opsonized yeast (p<0.01) with a small number of yeast that were engulfed by the cells (p<0.02). Further, endotoxin-treated cells showed an enhanced ability to reduce NBT dye (p<0.03). Therefore, we concluded that endotoxins of enteric pathogens are neutrophil chemotactic factors.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6899-6904
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• 2014

NGAL (neutrophil gelatinase-associated lipocalin) is a novel cancer-related protein involves multiple functions in many cancers and other diseases. We previously overexpressed NGAL to analyze its role in esophageal squamous cell carcinoma (ESCC). In this study, a protein-protein interaction (PPI) was constructed and the shortest paths from NGAL to transcription factors in the network were analyzed. We found 28 shortest paths from NGAL to RELA, most of them obeying the principle of extracellular to cytoplasm, then nucleus. These shortest paths were also prioritized according to their normalized intensity from the microarray by the order of interaction cascades. A systems approach was developed in this study by linking differentially expressed genes with publicly available PPI data, Gene Ontology and subcellular localizaton for the integrated analyses. These shortest paths from NGAL to DEG transcription factors or other transcription factors in the PPI network provide important clues for future experimental identification of new pathways.

• Journal of Radiation Protection and Research
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• v.33 no.3
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• pp.93-97
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• 2008

The purpose of this study reported here was to investigate the ability of Bu-Zhong-Yi-Qi-Tang (BZYQT), known to elevate hematopoietic functions, to protect mice undergoing treatment with whole body single gamma-irradiation. BZYQT was given (25 mg/kg B.W.) intraperitoneally at 36 and 12 hours before irradiation and 30 minute and 24 hours after irradiation. Recovery of neutrophil and lymphocyte counts was significantly stimulated by extract of BZYQT. Stimulated recovery by the extract from the BZYQT was also observed in thrombocyte. However, the anti-radiation effect of erythrocyte, hemoglobin and hematocrit was not as significant as that of leukocyte. Further studies are needed to better characterize the protective nature of BZYQT extract and its ingredients.

• Journal of Life Science
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• v.12 no.1
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• pp.14-18
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• 2002

Subpopulations of nucleotides that bind specifically to a variety of proteins have been isolated from a population of random sequence RNA/DNA molecules. Roughly one in $10^{13}$ random sequence RNA/DNA molecules folds in such a way as to create a specific binding site for small ligands. Since the development of in vitro selection procedure, more than 50 nucleic acid ligands (aptamers) have been isolated. These molecules are very useful for the study of molecular recognition between nucleic acid and protein/organic compound. In addition to these basic studies this method gives us a dream to produce new drugs against several diseases. We focused on several aptamers which specifically binds to trypsin-like serine proteases (thrombin, human neutrophil elastase, activated protein C and NS3 protease of human hepatitis C virus) and want to introduce their structural characteristics and some functions.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.57-57
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• 2003

In growing number of diseases it has been shown that aggregation of specific proteins has an important role in pathogenesis of the disorder. This has been demonstrated in structural details with the liver cirrhosis of ${\alpha}$$_1$-antitrypsin deficiency, and it is now believed that similar protein aggregation underlies many neurodegenerative disorders such as autosomal dominant Parkinson disease, prion diseases, Alzheimer disease, and Huntington disease. ${\alpha}$$_1$-Antieypsin, a member of serine pretense inhibitor (serpin) family, functions as an inhibitor of neutrophil elastase.

• Tuberculosis and Respiratory Diseases
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• v.69 no.4
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• pp.256-264
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• 2010

Background: According to the notion of the immunoregulatory functions of moxifloxacin (MFX), the effect of MFX on the neutrophilic respiratory burst in conjunction with the expression of cytosolic phospholipase $A_2$ ($cPLA_2$) was investigated. Methods: The effects and possible mechanisms of MFX on neutrophilic respiratory burst in oleic acid (OA)-induced acutely injured rats lung and OA-stimulated, isolated murine neutrophils were probed, associated with the expression of cytosolic phospholipase $A_2$ in vivo and in vitro. Results: In the OA-induced acutely-injured lungs, neutrophils were accumulated, which was attenuated by MFX. The parameters denoting a neutrophilic respiratory burst, such as nitro blue tetrazolium reaction, cytochrome-c reduction, neutrophil aggregation, $H_2O_2$ production in neutrophils revealed increased neutrophilic respiratory burst by OA, and MFX decreased all of these parameters. In addition, the enhanced expression of $cPLA_2$ in the lung and isolated murine neutrophils by OA were decreased by MFX. Conclusion: MFX suppresses the OA-induced neutrophilic respiratory burst by the suppression of $cPLA_2$ in neutrophils.

• Tuberculosis and Respiratory Diseases
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• v.71 no.3
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• pp.172-179
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• 2011

Background: Statins can regulate the production of pro-inflammatory cytokines and inhibit MMP production or activation in a variety of types of cells. This study evaluated whether statins would inhibit MMP release from human lung fibroblasts, which play a major role in remodeling processes. Methods: This study, using an in-vitro model (three-dimensional collagen gel contraction system), evaluated the effect of cytokines (tumor necrosis factor-${\alpha}$, TNF-a and interleukin-$1{\beta}$, IL-1b) on the MMP release and MMP activation from human lung fibroblasts. Collagen degradation induced by cytokines and neutrophil elastase (NE) was evaluated by quantifying hydroxyproline. Results: In three-dimensional collagen gel cultures (3D cultures) where cytokines (TNF-a and IL-1b) can induce the production of MMPs by fibroblasts, it was found that simvastatin inhibited MMP release. In 3D cultures, cytokines together with NE induced collagen degradation and can lead to activation of the MMP, which was inhibited by simvastatin. Conclusion: Simvastatin may play a role in regulating human lung fibroblast functions in repair and remodeling processes by inhibiting MMP release and the conversion from the latent to the active form of MMP.

• Journal of Haehwa Medicine
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• v.9 no.1
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• pp.215-223
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• 2000

To understand immunopharmacologic effects on Cervi Pantotrichum Cornu, Morindae Officinalis Radix, Cistanches Herba, Curculginis Rhizoma, Epimedii Herba, Eucommiae Cortex, we investigated chinese experimental documents, and we could reach conclusions as follows : 1. The effects on cell-mediated immune system were as follows. 1) The effects on macrophage (1) The herbal medicines promoting to increase the number of WBC in the peripheral blood were Morindae Officinalis Radix, Epimedii Herba and that promoting to reinforce the phagocytic functions of neutrophil was Curculginis Rhizoma. (2) The herbal medicines promoting the phagocytic functions of mononuclear, macrophage were Cervi Pantotrichum Cornu, Cistanches Herba, Eucommiae Cortex. 2) The herbal medicines stimulating the activities of T lymphocytes were Cervi Pantotrichum Cornu, Curculginis Rhizoma, Epimedii Herba, Eucommiae Cortex. 2. The effects on humoral immune system were as follows. 1) The herbal medicines increasing the activity of complement receptor were Cervi Pantotrichum Cornu, Curculginis Rhizoma. 2) The herbal medicines reinforcing immunity of spleen cells were Cervi Pantotrichum Cornu, Cistanches Herba, Epimedii Herba. 3) The herbal medicines promoting proliferation of spleen cells that produce antibody after having been immunized by SRBC were Cervi Pantotrichum Cornu, Cistanches Herba, Epimedii Herba. 3. The herbal medicines, reinforcing immunity on delayed type hypersensitivity were Cervi Pantotrichum Cornu, Cistanches Herba, Eucommiae Cortex. As you know in the many bibliological documents, the studies on the effects of Drugs for Tonifying Yang were started along right lines. Recently the studies on those were accomplished more rapidly and applied many immune diseases. We thought that Drugs for Tonifying Yang could be important immunopotentiators. Therefore we can apply those herbal medicines not only to immune diseases but also inflammatory diseases, senile infirmity and all sorts of tumor.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.54-54
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• 2003

The activation of protooncogenes or the inactivation of their gene products may be a specific and effective functional study for human neoplasia. To examine this possibility, we have used the tetracycline regulatory system to generate transgenic mice that conditionally express the HccR-2 protooncogene in vivo. The new human cervical cancer protooncogene (HccR-2) was detected from cervical cancer cell line. To elucidate its biological functions, we generated transgenic mice that expressed the HccR-2 gene. The sustained expression of the HccR-2 transgene culminated chronic neutrophilic leukemia (CNL). CNL is a rare chronic myeloproliferative disorder that presents as a sustained, mature neutrophilic leukocytosis with few or no circulating immature granulocytes, the absence of peripheral blood monocytosis, basophilia, or eosinophilia, and infiltration of neutrophils at the liver, spleen and kidney. Mice expressing the HccR-2 and tetracycline-transactivating protein (tTa) transgene were found to have altered myeloid development that was characterized by increased percentages of mature neutrophil and band form neutrophil in the peripheral blood, liver and spleen. Activation of the transgene causes CNL. In our model, expression of HccR-2 transgene mice was similar in many respects to the human CNL. This model will be valuable not only for investigating the biological properties of the HccR-2 and other protooncogenes in vivo but also for analyzing the mechanism involved in the progression of CNL.

• Tuberculosis and Respiratory Diseases
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• v.57 no.3
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• pp.250-256
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• 2004

Background : Bacterial infections in diabetic patients are an important cause of increased morbidity and mortality. It has been reported that bacterial infections in diabetics showed more impaired PMN functions such as reduced PMN respiratory burst and decreased microbicidal activity in inflammed tissues. Also, apoptosis(programmed cell death) is postulated to be a key mechanism for neutrophil elimination. It is very important that PMN apoptosis keeps the balance from an area of inflammation. Actuallly, as little was known about PMN apoptosis and respiratory burst in diabetes, we investigated PMN apoptosis and hydrogen peroxide production after endotoxin exposure. Methods : Peripheral venous blood samples were collected by routine venipuncture from healthy volunteers and diabetics to harvest neutrophils. We respectively measured the PMN apoptosis, the production of hydrogen peroxide, and the cell viability. Results : Normal neutrophils showed a tendency to decreased apoptosis after endotoxin treatment. In patients with diabetes, PMN apoptosis was significantly decreased compared with healthy controls. In addition, the LPS-induced neutrophils in diabetics demonstrated more decreased apoptosis. However, the production of hydrogen peroxide was not different between groups. Conclusion : These observations suggest that the decreased PMN apoptosis in diabetics with endotoxin exposure may also affect the increased susceptibility and severity of infections.