Seung-Yong Seong

Wide River Institute of Immunology, Seoul National University

Myeloid-derived suppressor cells (MDSCs) consist of monocytic (M-) MDSCs and polymorphonuclear (PMN-) MDSCs that contribute to an immunosuppressive environment in tumor-bearing hosts. However, research on the phenotypic and functional heterogeneity of MDSCs in tumor-bearing hosts and across different disease stage is limited. Here we subdivide M-MD...

Keratinocytes are pivotal cells in the pathogenesis of atopic dermatitis (AD) as much as Th2 cells. In this sense, regulation of pro-inflammatory features of keratinocytes might be useful for AD patients. P2X7R-mediated activation of NLRP3 inflammasome (N3I) in keratinocytes and myeloid cells plays crucial roles in AD. Nonetheless, inhibition of P2...

Alzheimer’s disease (AD) is the most common cause of dementia due to inflammatory neurodegeneration in the brain. Neuroinflammation caused by damage associated molecular pattern (DAMP: Aβ, ATP) leads to neuronal apoptosis. From our study HY209, a NCAIDs and a TGR5 agonist, inhibits neuroinflammation and neurodegeneration. In vitro, HY209 suppressed...

Amyloid β (Aβ) and/or ATP activate the NLRP3 inflammasome (N3I) via P2X7R in microglia, which is crucial in neuroinflammation in Alzheimer’s disease (AD). Due to polymorphisms, subtypes, and ubiquitous expression of P2X7R, inhibition of P2X7R has not been effective for AD. We first report that taurodeoxycholate (TDCA), a GPCR19 ligand, inhibited th...

Introduction: Typhoid incidence in children is higher in urban areas than in rural areas of Bangladesh. This study examined whether healthy urban children harboured higher levels of Salmonella genes than healthy rural children. Methodology: Stool samples from 140 children were studied: 70 from rural areas and 70 from urban metropolitan areas. R...

Sodium taurodeoxycholate (TDCA) has been investigated for various inflammatory disorders such as sepsis. We recently evaluated nonclinical safety profile of TDCA using rats infused intravenously. As a series of preclinical safety investigations, we further conducted toxicity studies with TDCA delivered to dogs via intravenous administration under G...

Amyloid β (Aβ) and/or ATP activates NLRP3 inflammasome (N3I) by P2 × 7R ion channel of microglia, which is crucial in neuroinflammation shown in Alzheimer’s disease (AD). Due to polymorphisms, subtypes, and ubiquitous expression of P2 × 7R, inhibition of P2 × 7R has not been effective for AD. We first report that GPCR19 is a prerequisite for P2 × 7...

The anti-inflammatory effects of HY209 have been identified in sepsis. However, the anti-inflammatory potential of HY209 in colitis has not yet been investigated. In here, we evaluated the therapy efficacy of HY209 in an acute colitis mice model which induced by using dextran sulfate sodium (DSS). Compare to vehicle mice, HY209 treated mice showed...

HY209 has been reported to be a ligand for the membrane G protein–coupled receptor, TGR5. HY209 could inhibit inflammatory responses in sepsis by increasing number of immunosuppressive myeloid-derived suppressor cells (MDSC), suggesting the potent role of HY209 in the treatment of atopic dermatitis (AD). Here HY209 was evaluated whether it controls...

Alzheimer’s disease (AD) is an inflammatory neurodegenerative condition characterized by deposition of amyloid beta (Abeta) in the brain and origins dementia. Neuronal apoptosis following neuroinflammation by Abeta impairs cognition and memory. In this study we focused on Taurodeoxyxcholate (TDCA) is an active bile acid derivative with potent anti-...

Type 2 diabetic nephropathy (T2DN) progresses with an increasingly inflammatory milieu, wherein various immune cells are relevant. Herein, we investigated the levels of myeloid-derived suppressor cells (MDSCs) and their clinical implication in patients with T2DN. A total of 91 subjects (T2DN, n=80; healthy, n=11) were recruited and their PBMCs were...

We aimed to identify novel biomarkers in amniotic fluid (AF) that predict the outcome of emergency cerclage in women with cervical insufficiency. This retrospective cohort study included 40 singleton pregnant women who received emergency cerclage for cervical insufficiency (17-25 weeks) and underwent amniocentesis. Label-free liquid chromatography-...

Urinary tract infection (UTI) is one of the most common bacterial infections in infants less than age 1 year. UTIs frequently recur and result in long-term effects include sepsis and renal scarring. Uropathogenic Escherichia coli (UPEC), the most prevalent organism found in UTIs, can cause host inflammation via various virulence factors including h...

Taurodeoxycholate (TDCA) inhibits various inflammatory responses suggesting potential clinical application. However, the toxicity of TDCA has not been evaluated in detail in vivo. We investigated the acute toxicity and 4-week repeated-dose toxicity of TDCA following intravenous infusion under Good Laboratory Practice regulations. In the sighting st...

Bile acids (BAs) control metabolism and inflammation by interacting with several receptors. Here, we report that intravenous infusion of taurodeoxycholate (TDCA) decreases serum pro-inflammatory cytokines, normalizes hypotension, protects against renal injury, and prolongs mouse survival during sepsis. TDCA increases the number of granulocytic myel...

Aim of the study: To identify proteins of which depletion are associated with the poor 6-month neurological outcome of out-of-hospital cardiac arrest survivors. Methods: Seven healthy volunteers and 34 out-of-hospital cardiac arrest survivors admitted to the intensive care unit (ICU) and underwent targeted-temperature management were enrolled. A...

Mitochondrial defects and anti-mitochondrial cardiolipin (CL) antibodies are frequently detected in autoimmune disease patients. CL from dysregulated mitochondria activates various pattern recognition receptors, such as NLRP3. However, the mechanism by which mitochondrial CL activates antigen-presenting cells (APCs) as a damage-associated molecular...

Myeloid-derived suppressor cells (MDSCs) are the heterogeneous population comprised of myeloid cell progenitors and precursors of granulocytes, macrophages and dendritic cells. In healthy individuals, Immature Myeloid Cells (IMCs) generated in the bone marrow differentiate into mature granulocytes, macrophages or dendritic cells. Pathological condi...

Amyotrophic lateral sclerosis (ALS) is a devastating human neurodegenerative disease. The precise pathogenic mechanisms of the disease remain uncertain, and as of yet, there is no effective cure. Human adipose stem cells (hASC) can be easily obtained during operative procedures. hASC have a clinically feasible potential to treat neurodegenerative d...

Most amyotrophic lateral sclerosis (ALS) patients show focal onset of upper and lower motor neuron signs and spread of symptoms to other regions or the other side clinically. Progression patterns of sporadic ALS are unclear. The aim of this study was to evaluate the pattern of respiratory deterioration in sporadic ALS according to the onset site by...

Comparison of growth factors between hASC and hASC extract. BDNF, VEGF, PDGF-1, IGF-1, HGF-α, FGF-2 were investigated in hASC or hASC extract by western blot. The results showed that both groups contained various growth factors similarly (BDNF, Brain-derived neurotrophic factor; VEGF, Vascular endothelial growth factor; PDGF-1, Platelet-derived gro...

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by selective degeneration of motor neurons. Mutant superoxide dismutase 1 (SOD1) is often found as aggregates in the cytoplasm in motor neurons of various mouse models and familial ALS patients. The interplay between motor neurons and astrocytes is crucial for diseas...

Cellular and morphological characterization of neurons and astrocytes enriched cultures. (A, B) Immunofluorescent staining for SOD1 of cortical neurons (red) and astrocytes (green) with DAPI for nuclei (blue). (C) Western blot analysis confirmed the presence of the human SOD1 in cortical neurons and astrocytes. Levels of hSOD1 in both mutant cortic...

ABSTRACT: Introduction: Split hand is considered to be a specific feature of amyotrophic lateral sclerosis (ALS). Methods: We evaluated the pattern difference of intrinsic hand muscles of upper limb-onset ALS (UL-ALS), upper limb-onset progressive muscular atrophy (UL-PMA), brachial amyotrophic diplegia (BAD), and Hirayama disease (HD) by measuring...

Reactive oxygen species (ROS) play an important role in cellular signaling as second messengers. However, studying the role of ROS in physiological redox signaling has been hampered by technical difficulties in controlling their generation within cells. Here, we utilize two inert components, a photosensitizer and light, to finely manipulate the gen...

Background: IFN-gene induction in hepatitis C virus infected hepatocytes is not well defined. Results: IRF-3, IRF-7, and NF-B transcribe type III IFNs. Treatment with IFN-reduced HCV RNA and miR122. Conclusion: IFN-gene regulation in HCV-infected hepatocytes is similar to immune cells. IFN-may exert antiviral activity by down-regulating miR122. Sig...

Background The application of vaccine adjuvants has been vigorously studied for a diverse range of diseases in order to improve immune responses and reduce toxicity. However, most adjuvants have limited uses in clinical practice due to their toxicity.Methods Therefore, to reduce health risks associated with the use of such adjuvants, we developed a...

The replication fork temporarily stalls when encountering an obstacle on the DNA, and replication resumes after the barrier is removed. Simultaneously, activation of the replication checkpoint delays the progression of S phase and inhibits late origin firing. Camptothecin (CPT), a topoisomerase I (Top1) inhibitor, acts as a DNA replication barrier...

Background: Climate change affects the survival and transmission of arthropod vectors as well as the development rates of vector-borne pathogens. Increased international travel is also an important factor in the spread of vector-borne diseases (VBDs) such as dengue, West Nile, yellow fever, chikungunya, and malaria. Dengue is the most important ve...

Amplification of OBP, ND5, and COI. Lanes M, marker DNA (25- and 100-bp mixed DNA ladder); 1, Sample 1; 2, Sample 2; 3, Sample 3. (TIF)

Adaptation of tumor cells to the host is a major cause of cancer progression, failure of therapy, and ultimately death. Immune selection drives this adaptation in human cancer by enriching tumor cells with a cancer stem cell-like (CSC-like) phenotype that makes them resistant to CTL-mediated apoptosis; however, the mechanisms that mediate CSC maint...

Background and purpose: Lipopolysaccharide (LPS) induces intestinal dysmotility by alteration of smooth muscle and enteric neuronal activities. However, there is no report on the modulatory effects of LPS on the interstitial cells of Cajal (ICCs). We investigated the effect of LPS and its signal transduction in ICCs. Methods: We performed whole-...

Dying cells interact with living cells and release molecules that can signal to immune system. Based on the morphology of the dying cells, there are three types of cell death, which are apoptotic cell death (Type I), autophagic cell death (Type II) and necrotic cell death (Type III). The immune response is different according to the pathway of cell...

Dendritic cell-based cancer immunotherapy requires tumour antigens to be delivered efficiently into dendritic cells and their migration to be monitored in vivo. Nanoparticles have been explored as carriers for antigen delivery, but applications have been limited by the toxicity of the solvents used to make nanoparticles, and by the need to use tran...

Keratocytes are the first component to contact ocular pathogens when the epithelial barrier breaks down and the emerging evidences indicated keratocytes appeared to be one of the corneal cellular immune components. Little is known about the role of Toll-like receptors (TLRs) in keratocytes, although it has been well documented that keratocytes cons...

DNA vaccines have emerged as an attractive approach to generate antigen-specific T-cell immune response. Nevertheless, the potency of DNA vaccines still needs to be improved for cancer immunotherapy. In this study, we explored whether functional linkage of a Th1-polarizing chemokine, IP-10, to a model tumor antigen, human papillomavirus type 16 (HP...

Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of Scrub typhus. The control mechanisms for bacterial gene expression are largely unknown. Here, the global gene expression of O. tsutsugamushi within eukaryotic cells was examined using a microarray and proteomic approaches for the first time. These approaches iden...

Orientia tsutsugamushi, the causative agent of scrub typhus, is an obligate intracellular pathogen. Previously, we reported that the 56-kDa type-specific antigen (TSA56), a major outer membrane protein of O. tsutsugamushi, binds to fibronectin and facilitates bacterial entry into the host cell, potentially via an interaction with integrins. Here, w...

Dendritic cell (DC)-based vaccines have become a promising modality in cancer immunotherapy. However, their ability to initiate tumor antigen-specific T cell immunity is limited in various negative-feedback mechanisms. The rapid down-regulation of chemokines, such as the interferon inducible protein of 10 kDa (IP-10), which chemoattracts activated...

Both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) activate antigen-presenting cells, often through the same pattern recognition receptors (PRR), such as Toll-like receptors (TLR). The TLR4-CD14-MD2 and TLR2-CD14 complexes have been shown to play a role in the recognition of lipopolysaccharide (LPS)...

We suggested earlier that the hydrophobic portions (Hyppos) of molecules, which are normally embedded in the membranes of cells or the core of molecular structures so as to be separated from the aqueous environment, might serve as evolutionarily ancient alarm signals of injury or stress to initiate innate immune responses when they are exposed on t...

Carcinoembryonic antigen (CEA) is over-expressed on various human cancer cells and has been the target of immunotherapies using dendritic cells (DCs) pulsed with CEA-specific RNA or peptides, or transduced by CEA-expressing adenovirus or vaccinia virus. Because activated DCs do not phagocytose soluble protein antigens efficiently and pure immature...

Mucin antigen 1 (MUC1) is overexpressed on various human adenocarcinomas and haematological malignancies and has long been used as a target antigen for cancer immunotherapy. Most of the preclinical and clinical studies using MUC1 have used the tandem repeat region of MUC1, which could be presented by only a limited set of major histocompatibility c...

This study was undertaken to investigate the types and concentrations of microbial agents in various medical wastes as well as to characterize their survivals in these wastes at different temperatures for microbial risk assessment. Medical wastes collected from 5 major hospitals in South Korea were classified and stored at three different temperatu...

Part of pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern (DAMP) activate antigen-presenting cells through Toll-like receptors (TLRs) to initiate immune responses. However, controversy remains if TLR4 mediates DAMP signaling due to the confounding effects of potential LPS contamination. To test if TLR4 functions a...

Dendritic cells (DCs) induce innate immune responses by recognizing bacterial LPS through TLR4 receptor complexes. In this study, we compared gene expression profiles of TLR4 knockout (TLR4(neg)) DCs and wild type (TLR4(pos)) DCs after stimulating with LPS. We found that the expression of various inflammatory genes by LPS were TLR4-independent. Amo...

Rac is a protein involved in the various functions of macrophages (Mphi), including the production of reactive oxygen species (ROS), phagocytosis, chemotaxis and the secretion of cytokines (such as gamma-INF). This study tested the effects of nucleosides containing 8-oxoguanine(8-hydroxyguanine) such as 8-oxo-2'-guanosine (8-oxoG) or 8-oxo-2'-deoxy...

Dendritic cells (DCs) have become an important measure for the treatment of malignancies. Current DC preparations, however, generate short-lived DCs because they are subject to cell death from various apoptotic pressures. Antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) is one of the main obstacles to limit the DC-mediated immune priming since...

Author Summary Herpesvirus persists in its host by entering a latent state, periodically reactivating to produce infectious viral particles. Some of the herpesviruses have also been known to be related to cancers. Herpesvirus saimiri (HVS), an oncogenic monkey herpesvirus, persists in the T lymphocytes of its natural host, the squirrel monkey, with...

Secondary structure prediction of the N-terminal region of Tip from Herpevirus saimiri strains and Tio from Herpesvirus ateles, performed using PSIPRED (http://bioinf.cs.ucl.ac.uk/psipred/psiform.html). The predicted amphipathic helix (red box) and the transmembrane domain (blue box) are indicated. (0.14 MB PDF)

Quantitative analysis of binding between peptides and lipids. Numerical densitometric values obtained from Figure 5B were plotted as percentages of the maximum binding of peptides to each lipids (the highest value, for peptide binding to 100 pmol of lipids, was arbitrarily assigned “100% binding”). To estimate the saturated binding, 3-parameter sig...

Quantification of colocalization of Tip wt211-256, Tip amp1211-256, and Tip CD71TM211-256 with early endosomes or late endosome/lysosomes. Jurkat T cells expressing the GFP-fusion proteins were analyzed for colocalization with EEA1 or LAMP2 as described in Fig. 4A (A). In addition, HeLa cells expressing the GFP-fusion proteins were also analyzed fo...

TM domain amino acids contributing to lipid raft association, identified by alanine scan mutagenesis. (A) Sequences of wild type Tip, and its mutants carrying alanine scan mutations in their TM domain. (B) 293T cells transiently expressing wild type Tip or its mutants were lysed and processed for lipid raft fractionation. Proteins from each fractio...

Schematic representation of GFP fusion proteins of wild type or mutant Tip. In GFP-Tip amp2, which is not shown here, the positively-charged amino acids of the amphipathic helix are point-mutated into alanine (Figure 2A). (0.05 MB PDF)

Lipid raft association of flag-tagged Tip or its deletion mutant. 293T cells were transfected with plasmids encoding Tip or its deletion mutants as flag-tagged proteins, and processed for lipid raft fractionation. Proteins from each fraction of the sucrose gradient were subjected to immunoblotting with an anti-flag antibody to detect Tip or its mut...

Quantification of colocalization of Tip wt and Tip amp1 with early endosomes, late endosome/lysosomes, or CD3ζ. Jurkat T cells electroporated with plasmids encoding Tip or Tip amp1 were analyzed for Tip, Tip amp1, EEA1, LAMP2, CD3ζ colocalization as described in Fig. 3B. Pearson coefficient (R) values were obtained from 10 to 20 cells as described...

Size changes of liposomes following addition of amphipathic peptides. For the quantitative analysis of liposome tubulation, a laser light scattering assay was used, in which the morphological changes are estimated indirectly by measuring the size changes of liposomes. The liposomal size distribution was significantly altered by the addition of the...

The effect of mutations in amphipathic helix or transmembrane domain of Tip on the membrane association. The efficiency of membrane association of Tip and its mutants were measured by comparing the ratio of the proteins in whole cell lysate (WCL) and membrane-enriched fraction (MF). GFP fusion proteins in the 2% of WCL or 10% of MF were detected by...

To elucidate the roles of 8-hydroxydeoxyguanosine (oh(8)dG), the nucleoside of 8-hydroxyguanine (oh(8)Gua), we examined the effects of oh(8)dG upon LPS-induced intercellular adhesion molecule-1 (ICAM-1) expression and the underlying mechanisms in brain microglial cells. We found that oh(8)dG reduces LPS-induced reactive oxygen species (ROS) product...

Living organisms are composed of millions different kinds of molecules. Both hydrophilic and hydrophobic molecules make up cells and tissues. However, in healthy tissues, hydrophobic portions (hyppos) are seldom exposed on the surface of the biological molecules and supramolecular organization. Since the water-insoluble molecules could form non-pro...

To understand the pathogenesis of scrub typhus, we examined chemokine and cytokine production in susceptible (C3H/HeN) and resistant (BALB/c) mice after infection with O. tsutsugamushi Gilliam. C3H/HeN mice produced high levels of chemokines macrophage inflammatory proteins 1 alpha (MIP-1 alpha ), MIP-2, monocyte chemoattractant protein 1 (MCP-1),...

It is currently thought that immune responses are initiated by pathogen-associated molecular patterns or by tissue-derived danger/alarm signals. Here, we propose that these two groups of molecules might not be mutually exclusive. Many of them might be part of an evolutionarily ancient alert system in which the hydrophobic portions of biological mol...

gp96 plays a central role in innate as well as acquired immunity, maturation and chemotaxis of dendritic cells, Ab production, and cross-priming, and is a peptide acceptor in endoplasmic reticulum and an accessory to peptide loading of MHC class I molecules. The remarkable conservation of essential immunological properties of gp96 suggests their im...

Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of scrub typhus which is histopathologically characterized by inflammatory manifestations, indicating that rickettsiae induce mechanisms that amplify the inflammatory response. To understand the pathogenesis of scrub typhus, we examined chemokine and cytokine produc...

Sequencing of the human genome revealed that more than 30 000 genes encode proteins comprising the human proteome. "Proteomics" can be defined as a field of research studying proteins in terms of their function, expression, structure, modification and their interaction in physiological and in pathological states. The concentration, modification and...

Human macrophage chemoattractant protein 1 (MCP-1) is a potent mediator of macrophage migration and therefore plays an essential role in early events of inflammation. In endothelial cells, at least three independent pathways regulate MCP-1 expression by NF-kappaB and AP-1. Orientia tsutsugamushi causes vasculitis in humans by replicating inside mac...

Orientia tsutsugamushi shows both pro- and antiapoptotic activities in infected vertebrate cells. Apoptosis of THP-1 cells induced by beauvericin was inhibited by O. tsutsugamushi infection. Beauvericin-induced calcium redistribution was significantly reduced and retarded in cells infected with O. tsutsugamushi. Antiapoptotic activities of O. tsuts...

Optimizing conditions for the microarraying of protein antigens onto glass slides were studied. Various vendors, surface functional groups, buffers, and fixatives were evaluated to enhance protein binding. A total of 125 pg of human immunoglobulin was detectable with this assay system, suggesting that protein microarray can be applied for routine i...

The global use of a capsular polysaccharide-based pneumococcal vaccine has been limited because of serotype-specific protection and poor effectiveness in individuals with low immunocompetency. The mucosal immune system develops earlier in infants and lasts longer in the elderly than does the systemic immune system. Furthermore, mucosal immunization...