• Journal of Microbiology and Biotechnology
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• v.27 no.4
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• pp.709-717
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• 2017

Mucosal tissues are the initial site through which most pathogens invade. As such, vaccines and adjuvants that modulate mucosal immune functions have emerged as important agents for disease prevention. Herein, we investigated the immunomodulatory mechanisms of the B subunit of Escherichia coli heat-labile enterotoxin type IIa ($LT-IIa-B_5$), a potent non-toxic mucosal adjuvant. Alternations in gene expression in response to $LT-IIa-B_5$ were identified using a genome-wide transcriptional microarray that focused on dendritic cells (DC), a type of cell that broadly orchestrates adaptive and innate immune responses. We found that $LT-IIa-B_5$ enhanced the homing capacity of DC into the lymph nodes and selectively regulated transcription of pro-inflammatory cytokines, chemokines, and cytokine receptors. These data are consistent with a model in which directional activation and differentiation of immune cells by $LT-IIa-B_5$ serve as a critical mechanism whereby this potent adjuvant amplifies mucosal immunity to co-administered antigens.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.298-306
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• 2017

Background: Compound K (CK) is a bioactive derivative of ginsenoside Rb1 in Panax ginseng (Korean ginseng). Its biological and pharmacological activities have been studied in various disease conditions, although its immunomodulatory role in innate immunity mediated by monocytes/macrophages has been poorly understood. In this study, we aimed to elucidate the regulatory role of CK on cellular events mediated by monocytes and macrophages in innate immune responses. Methods: The immunomodulatory role of CK was explored by various immunoassays including cell-cell adhesion, fibronectin adhesion, cell migration, phagocytic uptake, costimulatory molecules, reactive oxygen species production, luciferase activity, and by the measurement of mRNA levels of proinflammatory genes. Results: Compound K induced cell cluster formation through cell-cell adhesion, cell migration, and phagocytic activity, but it suppressed cell-tissue interactions in U937 and RAW264.7 cells. Compound K also upregulated the surface expression of the cell adhesion molecule cluster of differentiation (CD) 43 (CD43) and costimulatory molecules CD69, CD80, and CD86, but it downregulated the expression of monocyte differentiation marker CD82 in RAW264.7 cells. Moreover, CK induced the release of reactive oxygen species and induced messenger RNA expression of proinflammatory genes, inducible nitric oxide synthase, and tumor necrosis factor-alpha by enhancing the nuclear translocation and transcriptional activities of nuclear factor kappa-B and activator protein-1. Conclusion: Our results suggest that CK has an immunomodulatory role in innate immune responses through regulating various cellular events mediated by monocytes and macrophages.

• Restorative Dentistry and Endodontics
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• v.48 no.2
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• pp.20.1-20.13
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• 2023

This mini-review was conducted to present an overview of the use of exosomes in regenerating the dentin-pulp complex (DPC). The PubMed and Scopus databases were searched for relevant articles published between January 1, 2013 and January 1, 2023. The findings of basic in vitro studies indicated that exosomes enhance the proliferation and migration of mesenchymal cells, as human dental pulp stem cells, via mitogen-activated protein kinases and Wingless-Int signaling pathways. In addition, they possess proangiogenic potential and contribute to neovascularization and capillary tube formation by promoting endothelial cell proliferation and migration of human umbilical vein endothelial cells. Likewise, they regulate the migration and differentiation of Schwann cells, facilitate the conversion of M1 pro-inflammatory macrophages to M2 anti-inflammatory phenotypes, and mediate immune suppression as they promote regulatory T cell conversion. Basic in vivo studies have indicated that exosomes triggered the regeneration of dentin-pulp-like tissue, and exosomes isolated under odontogenic circumstances are particularly strong inducers of tissue regeneration and stem cell differentiation. Exosomes are a promising regenerative tool for DPC in cases of small pulp exposure or for whole-pulp tissue regeneration.

• KSBB Journal
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• v.27 no.5
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• pp.295-300
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• 2012

Matured dendritic cells (DCs) begin migration with their release from the bone marrow (BM) into the blood and subsequent traffic into peripheral lymphoid and non-lymphoid tissues. Throughout this long movement, migrating DCs must apply specialized skills to reach their target destination. Non-invasive in vivo cell-tracking techniques are necessary to advance immune cell-based therapies. In this study, we used a DiD cell-tracking solution for in vivo dendritic cell tracking in naive mice. We tracked DiD (non-invasive fluorescence dye)-labeled mature dendritic cells using the Near Infrared (NIR) imaging system in normal mice. We examined the immunophenotype of DiD-labeled cells compared with non-labelled mature DCs, and obtained time-serial images of NIR-DC trafficking after mouse footpad injection. In conclusion, we confirmed that DiD-labeled DCs migrated into the popliteal lymph node 24 h after the footpad injection. Here, these data suggested that the cell tracking system with the stable fluorescence dye DiD was useful as a cell tracking tool to advance dendritic cell-based immunotherapy.

• IMMUNE NETWORK
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• v.10 no.1
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• pp.5-14
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• 2010

Background: There have been several reports describing the capability of ginseng extracts as an adjuvant. In this study, we tested if ginsan, a polysaccharide extracted from Panax ginseng, was effective in enhancing antibody response to orally delivered Salmonella antigen. Methods: Ginsan was treated before oral salmonella antigen administration. Salmonella specific antibody was determined by ELISA. mRNA expression was determined by RT-PCR. Cell migration was determined by confocal microscopy and flow cytometry. COX expression was detected by western blot. Results: Ginsan treatment before oral Salmonella antigen delivery significantly increased both secretory and serum antibody production. Ginsan increased the expression of COX in the Peyer's patches. Various genes were screened and we found that CCL3 mRNA expression was increased in the Peyer's patch. Ginsan increased dendritic cells in the Peyer's patch and newly migrated dendritic cells were mostly found in the subepithelial dome region. When COX inhibitors were treated, the expression of CCL3 was reduced. COX inhibitor also antagonized both the migration of dendritic cells and the humoral immune response against oral Salmonella antigen. Conclusion: Ginsan effectively enhances the humoral immune response to orally delivered antigen, mediated by CCL3 via COX. Ginsan may serve as a potent vaccine suppliment for oral immunization.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.481-486
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• 2013

Macrophages play a role in innate immune responses to various foreign antigens. Many products from primary tumors influence the activation and transmigration of macrophages. Here, we investigated a migration of macrophages stimulated with cancer cell culture-conditioned medium (CM). Macrophage activation by treatment with CM of B16F10 cells were judged by the increase in protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). The location where macrophages were at 4 h-incubation with control medium or CM was different from where they were at 5 h-incubation in culture dish. Percentage of superimposed macrophages at every 1 h interval was gradually increased by CM treatment as compared to control. Total coverage of migrated track expressed in coordinates was smaller and total distance of migration was shorter in CM-treated macrophages than that in control. Rac1 activity in CM-treated macrophages was also decreased as compared to that in control. When macrophages were treated with CM in the presence of dexamethasone (Dex), an increase in COX2 protein levels, and a decrease in Rac1 activity and total coverage of migration were reversed. In the meanwhile, biphasic changes were detected by Dex treatment in section distance of migration at each time interval, which was more decreased at early time and then increased at later time. Taken together, data demonstrate that macrophage motility could be reduced in accordance with activation in response to cancer cell products. It suggests that macrophage motility could be a novel marker to monitor cancer-associated inflammatory diseases and the efficacy of anti-inflammatory agents.

• Biomedical Science Letters
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• v.16 no.3
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• pp.179-185
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• 2010

Benzene is known as a ubiquitous air pollutant and has a carcinogenic influence on the human body. Benzene is also metabolized to other volatile organic compounds (VOCs) in the body such as phenol and hydroquinone (HQ). The metabolites are accumulated and further oxidized by myeloperoxidase in bone marrow. They act as toxic agents and cause a variety of diseases, including cancer, atopic dermatitis and asthma. In this study, we examined the effects of benzene and its metabolites on proliferation, differentiation and chemotaxis of EoL-1 cells, the human eosinophilic leukemia cell line. These chemicals had no effect on the proliferation of EoL-1 cells. Benzene decreased the differentiation of EoL-1 cells induced by butyric acid. HQ was induced the cell death during butyric acid-induced EoL-1 cell differentiation. In a chemotaxis experiment, benzene, phenol and HQ enhanced the cell migration induced by Lkn-1 but not by MCP-1, eotaxin, MIP-$1{\alpha}$ and RANTES. These findings provide the effect of VOCs on the regulation of eosinophil-involved immune response.

• Journal of the Korean Society of Visualization
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• v.19 no.1
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• pp.74-80
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• 2021

Cells regulate their shapes and motility by sensing the cues from the internal and external microenvironment. Under different circumstances, microglia, the brain resident immune cells, undergo dynamic phenotypic changes, one of which is a remarkable periodic oscillatory migration in vitro. However, very little is known about the kinematic and dynamic perspectives of this oscillatory behavior. In this study, we tracked the changes in cell morphology and nuclear displacement, and visualized the forces using traction force microscopy (TFM). By correlation analyses, we confirmed that the lamellipodia formation preceded the nuclear translocation. Moreover, traction, developed following lamellipodia formation, was found to be localized and fluctuated at two ends of the oscillating cells. Taken together, our results imply that oscillatory microglial cells feature a viscoelastic migration, which will contribute to the field of cell mechanics.

• BMB Reports
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• v.55 no.6
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• pp.267-274
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• 2022

Molecular imaging is used to improve the disease diagnosis, prognosis, monitoring of treatment in living subjects. Numerous molecular targets have been developed for various cellular and molecular processes in genetic, metabolic, proteomic, and cellular biologic level. Molecular imaging modalities such as Optical Imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Computed Tomography (CT) can be used to visualize anatomic, genetic, biochemical, and physiologic changes in vivo. For in vivo cell imaging, certain cells such as cancer cells, immune cells, stem cells could be labeled by direct and indirect labeling methods to monitor cell migration, cell activity, and cell effects in cell-based therapy. In case of cancer, it could be used to investigate biological processes such as cancer metastasis and to analyze the drug treatment process. In addition, transplanted stem cells and immune cells in cell-based therapy could be visualized and tracked to confirm the fate, activity, and function of cells. In conventional molecular imaging, cells can be monitored in vivo in bulk non-invasively with optical imaging, MRI, PET, and SPECT imaging. However, single cell imaging in vivo has been a great challenge due to an extremely high sensitive detection of single cell. Recently, there has been great attention for in vivo single cell imaging due to the development of single cell study. In vivo single imaging could analyze the survival or death, movement direction, and characteristics of a single cell in live subjects. In this article, we reviewed basic principle of in vivo molecular imaging and introduced recent studies for in vivo single cell imaging based on the concept of in vivo molecular imaging.

• BMB Reports
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• v.53 no.4
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• pp.181-190
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• 2020

Protein phosphatase 4 (PP4), one of serine/threonine phosphatases, is involved in many critical cellular pathways, including DNA damage response (DNA repair, cell cycle regulation, and apoptosis), tumorigenesis, cell migration, immune response, stem cell development, glucose metabolism, and diabetes. PP4 has been steadily studied over the past decade about wide spectrum of physiological activities in cells. Given the many vital functions in cells, PP4 has great potential to develop into the finding of key working mechanisms and effective treatments for related diseases such as cancer and diabetes. In this review, we provide an overview of the cellular and molecular mechanisms by which PP4 impacts and also discuss the functional significance of it in cell health.