Won-Ha Lee

Kyungpook National University, Daikyū, Daegu, South Korea

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Publications (88)282.75 Total impact

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    ABSTRACT: Recent neuroscience research has established the adult brain as a dynamic organ having a unique ability to undergo changes with time. Neuroglia, especially microglia and astrocytes, provide dynamicity to the brain. Activation of these glial cells is a major component of the neuroinflammatory responses underlying brain injury and neurodegeneration. Glial cells execute functional reaction programs in response to diverse microenvironmental signals manifested by neuropathological conditions. Activated microglia exist along a continuum of two functional states of polarization namely M1-type (classical/proinflammatory activation) and M2-type (alternative/anti-inflammatory activation) as in macrophages. The balance between classically and alternatively activated microglial phenotypes influences disease progression in the CNS. The classically activated state of microglia drives the neuroinflammatory response and mediates the detrimental effects on neurons, whereas in their alternative activation state, which is apparently a beneficial activation state, the microglia play a crucial role in tissue maintenance and repair. Likewise, in response to immune or inflammatory microenvironments astrocytes also adopt neurotoxic or neuroprotective phenotypes. Reactive astrocytes exhibit two distinctive functional phenotypes defined by pro- or anti-inflammatory gene expression profile. In this review, we have thoroughly covered recent advances in the understanding of the functional polarization of brain and peripheral glia and its implications in neuroinflammation and neurological disorders. The identifiable phenotypes adopted by neuroglia in response to specific insult or injury can be exploited as promising diagnostic markers of neuroinflammatory diseases. Furthermore, harnessing the beneficial effects of the polarized glia could undoubtedly pave the way for the formulation of novel glia-based therapeutic strategies for diverse neurological disorders.
    No preview · Article · Nov 2015 · Biochemical pharmacology
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    ABSTRACT: Bitter gourd is the fruit of a tropical vine in Asia, Africa, and South America where it is commonly used in traditional medicine. Our study tested the effects of a fermented extract of the bitter gourd on the inflammatory activities of the human monocytic leukemia cell line, THP-1. Treatment with the extract resulted in the suppression of phagocytic as well as lipopolysaccharide (LPS)-induced adhesion activity. Interestingly, the LPS-induced expression of matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) was suppressed by the extract while the expression of Interleukin-8 (IL-8) was upregulated. The extract inhibited the LPS-induced activation of p38 mitogen-activated protein kinase (MAPKs) and nuclear factor-κB (NF-κB), both of which are well known to be required for the expression of MMP-9 and TNF-α. In contrast, the expression of interferon regulatory factor (IRF) 1, a transcription factor involved in the expression of IL-8, but not TNF-α, was enhanced by the extract. Suppression of IRF-1 expression resulted in the elimination of the extract's interleukin-8 (IL-8) enhancing effect. These results indicate that the fermented bitter gourd extract has general anti-inflammatory effects, with a differential effect on the expression of cytokines through modulation of NF-κB and IRF-1 activities.
    No preview · Article · May 2015 · Animal cells and systems the official publication of the Zoological Society of Korea
  • Sang-Min Lee · Kyoungho Suk · Won-Ha Lee
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    ABSTRACT: MARCKS, a substrate of protein kinase C, is involved in various processes associated with cytoskeletal movement. Although the expression of MARCKS is highly induced in macrophages, its role in macrophage function has not been studied in detail. Notably, the suppression of MARCKS expression in macrophage cell lines blocked LPS-induced expression of TNF-α at the transcriptional level. Treatment of macrophages with MARCKS N-terminus sequence (MANS) and effector domain (ED) peptides, which mimic functional domains and block the phosphorylation of MARCKS, suppressed the LPS-induced expression of TNF-α through suppression of p38 and JNK MAPKs and NF-κB. Treatment of mice with MANS peptide reduced serum TNF-α and IL-6 levels and resulted in 40% survival of mice after the administration of a lethal dose of LPS. These data demonstrate that MARCKS is involved in the regulation of proinflammatory cytokine expression in macrophages and that MARCKS-derived peptides can be used to suppress inflammatory responses. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Apr 2015 · Cellular Immunology
  • Seok-Won Jang · Su-Geun Lim · Kyoungho Suk · Won-Ha Lee
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    ABSTRACT: Lymphotoxin-beta receptor (LTβR), a receptor for LIGHT and LTα1β2, is expressed on the epithelial, stromal, and myeloid cells. LTβR is known to affect the lymphoid organ development and immune homeostasis. However, its role in macrophage function has not been sufficiently elucidated. The effect of LTβR stimulation in the inflammatory activation of macrophages was investigated by treating the human macrophage-like cell line THP-1 with LTβR-specific monoclonal antibody. Interestingly, combined treatment with anti-LTβR antibody and LPS caused the synergistic induction of IL-8 expression at the transcriptional level. Analysis indicated that nuclear factor (NF)-κB activity was enhanced via the mitogen-activated protein kinase (MAPK) and glycogen synthase kinase (GSK)-3β/cAMP response element binding protein (CREB) pathways. In addition, LTβR stimulation induced the expression of interferon regulatory factor (IRF)-1, one of the major transcription factors of IL-8 gene. Down-regulation of IRF-1 expression reduced the enhancing effect caused by LTβR stimulation. This indicates that the LTβR stimulation enhances the LPS-induced expression of IL-8 via the combined action of NF-κB and IRF-1. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Apr 2015 · Immunology letters
  • Jae-Kwan Kim · Suk-Won Jang · Kyoungho Suk · Won-Ha Lee
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    ABSTRACT: Fascin is a well-known cytoskeletal regulatory protein that, as a substrate of protein kinase C (PKC), is involved in PKC-mediated translational regulation of TNF-α in macrophages stimulated with lipopolysaccharide (LPS). The regulatory effects of fascin targeted the 3'-untraslated region (UTR) of the TNF-α mRNA, and suppression of PKC activity or fascin expression resulted in specific blockage of the LPS-induced translational activation of the mRNA. In an effort to identify the molecular mechanism of this fascin-mediated translational regulation, the expression levels of micro-RNA (miRNA) after stimulation of the toll-like receptor 4 (TLR4) signaling pathways were analyzed in cells with down-regulation of fascin. The LPS-induced translation of TNF-α is known to be regulated by miR-155 and miR-125b, which have positive and negative effects, respectively. Interestingly, suppression of fascin expression reversed LPS-induced down-regulation of miR-125b and abolished the LPS-induced increase in miR-155. Furthermore, introduction of miR-155 precursor, blocking of miR-125b activity, or introduction of a mutation into the miR-125b binding site of the TNF-α 3'-UTR restored translational activation in cells with suppressed fascin expression. These data indicate that fascin regulates translation through miR-155 and miR-125b, which target 3' UTR in TNF-α mRNA.
    No preview · Article · Apr 2015 · Immunological Investigations
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    ABSTRACT: Lentiviral short hairpin RNA (shRNA)-mediated genetic screening is a powerful tool for identifying loss-of-function phenotype in mammalian cells. Here, we report the identification of 91 cell migration-regulating genes using unbiased genome-wide functional genetic selection. Individual knockdown or cDNA overexpression of a set of 10 candidates reveals that most of these cell migration determinants are strongly dependent on the PI3K/PTEN/AKT pathway and on their downstream signals, such as FOXO1 and p70S6K1. ALK, one of the cell migration promoting genes, uniquely uses p55γ regulatory subunit of PI3K, rather than more common p85 subunit, to trigger the activation of the PI3K-AKT pathway. Our method enables the rapid and cost-effective genome-wide selection of cell migration regulators. Our results emphasize the importance of the PI3K/PTEN/AKT pathway as a point of convergence for multiple regulators of cell migration.
    No preview · Article · Oct 2014 · Nature Communications
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    ABSTRACT: Lipocalin-2 (LCN2) plays an important role in cellular processes as diverse as cell growth, migration/invasion, differentiation, and death/survival. Furthermore, recent studies indicate that LCN2 expression and secretion by glial cells are induced by inflammatory stimuli in the central nervous system (CNS). The present study was undertaken to examine the regulation of LCN2 expression in experimental autoimmune encephalomyelitis (EAE), and to determine the role of LCN2 in the disease process. LCN2 expression was found to be strongly increased in spinal cord and secondary lymphoid tissues after EAE induction. In spinal cords, astrocytes and microglia were the major cell types expressing LCN2 and its receptor 24p3R, respectively, whereas in spleens, LCN2 and 24p3R were highly expressed in neutrophils and dendritic cells, respectively. Furthermore, disease severity, inflammatory infiltration, demyelination, glial activation, the expression of inflammatory mediators, and the proliferation of MOG-specific T cells were significantly attenuated in Lcn2-deficient mice as compared with wild-type animals. MOG-specific T cells in culture exhibited an increased expression of Il17a, Ifng, Rorc, and Tbet after treatment with recombinant LCN2 protein. Moreover, LCN2-treated glial cells expressed higher levels of pro-inflammatory cytokines, chemokines, and MMP-9. Adoptive transfer and recombinant LCN2 protein injection experiments suggested that LCN2 expression in spinal cord and peripheral immune organs contributes to EAE development. Taken together, these results imply LCN2 is a critical mediator of autoimmune inflammation and disease development in EAE, and suggest that LCN2 be regarded a potential therapeutic target in multiple sclerosis.
    Preview · Article · May 2014 · Journal of Biological Chemistry
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    ABSTRACT: Lipocalin-2 (LCN2) is an acute phase protein induced in response to injury, infection or other inflammatory stimuli. Based on the previously reported involvement of LCN2 in chemokine induction and in the recruitment of neutrophils at the sites of infection or tissue injury, we investigated the role of LCN2 in the pathogenesis of chronic/persistent inflammatory pain hypersensitivity. In the complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model, LCN2 expression was strongly induced in the ipsilateral hindpaws, peaking at 12hr after CFA injection and then gradually subsiding. In CFA-injected hindpaw tissues, LCN2 and its receptor 24p3R were mainly expressed in infiltrating neutrophils and macrophages. CFA-induced thermal hyperalgesia and mechanical allodynia were significantly diminished in Lcn2-deficient mice compared to wild-type animals. Furthermore, neutrophil infiltration, myeloperoxidase activity, expression of TNF-α, IL-1β and MIP-2 in CFA-injected hindpaws, and spinal glial activation were markedly reduced by Lcn2 deficiency. An intraplantar injection of recombinant LCN2 protein induced thermal and mechanical hypersensitivities in naïve mice, and this was accompanied by neutrophil and macrophage infiltration into the hindpaws and glial activation in the dorsal horn of the spinal cord. Taken together, our results show that inflammatory cell-derived LCN2 at the sites of inflammation plays important roles in central sensitization and the subsequent nociceptive behavior in the rodent model of chronic inflammatory pain.
    No preview · Article · Jan 2014 · Experimental Neurology
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    ABSTRACT: Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain.
    Preview · Article · Dec 2013 · Immune Network
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    ABSTRACT: Astrocytes provide structural and functional support for neurons, as well as display neurotoxic or neuroprotective phenotypes depending upon the presence of an immune or inflammatory microenvironment. This study was undertaken to characterize multiple phenotypes of activated astrocytes and to investigate the regulatory mechanisms involved. We report that activated astrocytes in culture exhibit two functional phenotypes with respect to pro- or anti-inflammatory gene expression, glial fibrillary acidic protein expression, and neurotoxic or neuroprotective activities. The two distinct functional phenotypes of astrocytes were also demonstrated in a mouse neuroinflammation model, which showed pro- or anti-inflammatory gene expression in astrocytes following challenge with classical or alternative activation stimuli; similar results were obtained in the absence of microglia. Subsequent studies involving recombinant lipocalin-2 (LCN2) protein treatment or Lcn2-deficient mice indicated that the pro- or anti-inflammatory functionally polarized phenotypes of astrocytes and their intracellular signaling pathway were critically regulated by LCN2 under in vitro and in vivo conditions. Astrocyte-derived LCN2 promoted classical proinflammatory activation of astrocytes but inhibited IL-4-STAT6 signaling, a canonical pathway involved in alternative anti-inflammatory activation. Our results suggest that the secreted protein LCN2 is an autocrine modulator of the functional polarization of astrocytes in the presence of immune or inflammatory stimuli and that LCN2 could be targeted therapeutically to dampen proinflammatory astrocytic activation and related pathologies in the CNS.
    Preview · Article · Oct 2013 · The Journal of Immunology
  • Su-Geun Lim · Kyoungho Suk · Won-Ha Lee
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    ABSTRACT: LIGHT is a type II transmembrane protein belonging to the TNF superfamily which is involved in co-stimulation of T cells or apoptosis in tumors. In this study, the possibility of LIGHT-mediated reverse signaling was tested in the human monocytic leukemia cell line, THP-1. For stimulation of LIGHT, cells were stimulated with specific monoclonal antibody and changes in macrophage-related functions such as phagocytosis, adhesion, migration, cytokine secretion, and production of pro-inflammatory mediators were tested. Triggering of LIGHT induced production of pro-inflammatory mediators such as interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 while suppressing the phagocytic activity. Utilization of signaling inhibitors and Western blot demonstrated that LIGHT activated ERK MAPK and PI3K and the major inflammatory transcription factor NF-κB. These data indicate that LIGHT-mediated signaling could modulate the macrophage activities and that successful regulation of its activity could be beneficial to the treatment of chronic inflammatory conditions where macrophages play an important role.
    No preview · Article · Aug 2013 · Cellular Immunology
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    ABSTRACT: Lipocalin 2 (LCN2), which is also known as 24p3 and neutrophil gelatinase-associated lipocalin (NGAL), binds small, hydrophobic ligands and interacts with cell surface receptor 24p3R to regulate diverse cellular processes. In the present study, we examined the role of LCN2 in the pathogenesis of neuropathic pain using a mouse model of spared nerve injury (SNI). Lcn2 mRNA levels were significantly increased in the dorsal horn of the spinal cord after SNI, and LCN2 protein was mainly localized in neurons of the dorsal and ventral horns. LCN2 receptor 24p3R was expressed in spinal neurons and microglia after SNI. Lcn2-deficient mice exhibited significantly less mechanical pain hypersensitivity during the early phase after SNI, and an intrathecal injection of recombinant LCN2 protein elicited mechanical pain hypersensitivity in naive animals. Lcn2 deficiency, however, did not affect acute nociceptive pain. Lcn2-deficient mice showed significantly less microglial activation and proalgesic chemokine (CCL2 and CXCL1) production in the spinal cord after SNI than wild-type mice, and recombinant LCN2 protein induced the expression of these chemokines in cultured neurons. Furthermore, the expression of LCN2 and its receptor was detected in neutrophils and macrophages in the sciatic nerve following SNI, suggesting the potential role of peripheral LCN2 in neuropathic pain. Taken together, our results indicate that LCN2 plays a critical role in the development of pain hypersensitivity following peripheral nerve injury and suggest that LCN2 mediates neuropathic pain by inducing chemokine expression and subsequent microglial activation.
    Preview · Article · Jul 2013 · Journal of Biological Chemistry
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    ABSTRACT: Jaceosidin is a naturally occurring flavone with pharmacological activity. Jaceosidin, as one of the major constituents of the medicinal herbs of the genus Artemisia, has been shown to exert anticancer, anti-oxidative, anti-inflammatory, and immunosuppressive effects. This study was undertaken to determine the effect of jaceosidin on microglia and neuroinflammation. Microglia are the innate immune cells in the central nervous system, and they play a central role in the initiation and maintenance of neuroinflammation. We report that jaceosidin inhibits inflammatory activation of microglia, reducing nitric oxide (NO) production and proinflammatory cytokine expression. IC(50) for NO inhibition was 27 ± 0.4 μM. The flavone also attenuated microglial neurotoxicity in the microglia/neuroblastoma co-culture. Systemic injection of jaceosidin ameliorated neuroinflammation in the mouse model of experimental allergic encephalomyelitis. These results indicate that plant flavone jaceosidin is a microglial inhibitor with anti-neuroinflammation activity. Copyright © 2012 John Wiley & Sons, Ltd.
    No preview · Article · Mar 2013 · Phytotherapy Research
  • Byong-Keol Min · Kyoungho Suk · Won-Ha Lee
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    ABSTRACT: Lysosome-associated membrane proteins (LAMPs), a family of highly glycosylated transmembrane proteins, are well known lysosomal markers. Recent investigations revealed the cell surface expression of LAMPs, especially after activation in various cell types. Although their role in lysosome function is under intense investigation, little is known about the function of this cell surface form of LAMPs. To investigate the role of cell surface LAMPs in macrophage activities, the human macrophage-like cell line THP-1 was stimulated with monoclonal antibodies specific to CD107a (LAMP-1) or CD107b (LAMP-2). Stimulation of CD107 enhanced LPS-induced IL-8 secretion and induced adhesion of THP-1 cells to culture plates coated with extracellular matrix proteins such as collagen, fibronectin, and laminin. Utilization of specific inhibitors of signaling adapters and Western blot analysis revealed that extracellular signal-regulated kinase (ERK) mediates the regulatory action of CD107. These results suggest that stimulation of THP-1 cells through CD107 affects macrophage-associated functions such as cytokine secretion and cellular adhesion through activation of ERK.
    No preview · Article · Feb 2013 · Cellular Immunology
  • Eun-Ju Kim · Kyoungho Suk · Won-Ha Lee
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    ABSTRACT: Background: Src homology 2 domain-containing protein tyrosine phosphatase substrate (SHPS)-1 is known to have regulatory effects on myeloid cells. However, its role in macrophage activation is not clearly understood. Methods and results: In order to investigate the role of SHPS-1 in Toll-like receptor (TLR)-mediated activation, human monocytic cell lines were treated with anti-SHPS-1 monoclonal antibody. The triggering of SHPS-1 blocked the expression of IL-8 and TNF-α in cells treated with a TLR4 ligand that induces a signaling pathway involving myeloid differentiation factor 88 (MyD88) and Toll-interleukin-1 receptor (TIR)-domain-containing adapter-inducing interferon-β (TRIF). Interestingly, SHPS-1 inhibited TLR9/MyD88-mediated, but not TLR3/TRIF-mediated, expression of IL-8. Accordingly, a synthetic peptide representing the immunoreceptor tyrosine-based inhibition motif (ITIM) of SHPS-1 suppressed only the MyD88 pathway. Utilization of specific inhibitors and Western blot analysis indicated that the inhibitory effects were mediated by Src homology 2 domain-containing phosphatases (SHPs) and phosphoinositide 3-kinase (PI3K). Conclusion: SHPS-1 negatively regulates the MyD88-dependent TLR signaling pathway through the inhibition of NF-κB activation.
    No preview · Article · Jan 2013 · Agents and Actions
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    ABSTRACT: Activated macrophages are classified into two different forms: classically activated (M1) or alternatively activated (M2) macrophages. The presence of M1/M2 phenotypic polarization has also been suggested for microglia. Here, we report that the secreted protein lipocalin 2 (LCN2) amplifies M1 polarization of activated microglia. LCN2 protein (EC(50) 1 μg/ml), but not glutathione S-transferase used as a control, increased the M1-related gene expression in cultured mouse microglial cells after 8-24 h. LCN2 was secreted from M1-polarized, but not M2-polarized, microglia. LCN2 inhibited phosphorylation of STAT6 in IL-4-stimulated microglia, suggesting LCN2 suppression of the canonical M2 signaling. In the lipopolysaccharide (LPS)-induced mouse neuroinflammation model, the expression of LCN2 was notably increased in microglia. Primary microglial cultures derived from LCN2-deficient mice showed a suppressed M1 response and enhanced M2 response. Mice lacking LCN2 showed a markedly reduced M1-related gene expression in microglia after LPS injection, which was consistent with the results of histological analysis. Neuroinflammation-associated impairment in motor behavior and cognitive function was also attenuated in the LCN2-deficient mice, as determined by the rotarod performance test, fatigue test, open-field test, and object recognition task. These findings suggest that LCN2 is an M1-amplifier in brain microglial cells.-Jang, E., Lee, S., Kim, J.-H., Kim, J.-H., Seo, J.-W., Lee, W.-H., Mori, K., Nakao, K., Suk, K. Secreted protein lipocalin-2 promotes microglial M1 polarization.
    Preview · Article · Dec 2012 · The FASEB Journal
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    ABSTRACT: The genomes of three South Korean Rinderpest virus vaccine strains (L72, LA77, and LA96) were analyzed in order to investigate their genetic variability. These three vaccine strains were all derived from the same virus strain origin (Fusan) through repeated passages in different culture systems. The full genome length of the three strains was 15,882 nucleotides, and the sequence similarity between the three South Korean RPV strains at the nucleotide level was 98.1 to 98.9%. The genetic distance between Nakamura III, L72, LA77, LA96, and LATC06 and the Kabete strain was greater than that between the Fusan and Kabete strains for the P, V, and C genes. The difference in pathogenicity among these strains might be due to the V gene, which has a positive (>1) selection ratio based on the analysis of synonymous (dS) and nonsynonymous (dN) substitution rates (dN/dS ratio [ω]).
    Preview · Article · Dec 2012 · Journal of Virology
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    ABSTRACT: A multiplex reverse transcription polymerase chain reaction (mRT-PCR) assay was developed for the simultaneous detection of canine distemper virus (CDV), canine respiratory coronavirus (CRCoV), and canine influenza virus (CIV). These viral pathogens are all causative agents of canine infectious respiratory disease (CIRD). The sensitivity and specificity of the mRT-PCR were determined by comparing it to a rapid antigen test (RAT) or immuno-chromatography test kit and reverse transcription-polymerase chain reaction (RT-PCR) in the detection of CDV, CRCoV, and CIV antigens present in 100 clinical samples (nasal swabs and whole blood samples) from 50 dogs with respiratory disease symptoms. This study revealed that mRT-PCR had almost exactly the same performance or results were almost 100% in agreement with that of RT-PCR and RAT both in terms of the assay sensitivity and specificity which was more highly evident in detecting CIV, CDV, and CRCoV antigens present in canine nasal swab samples. Therefore, this assay could be a better alternative for the definitive and simultaneous ante-mortem detection of the three viral pathogens that cause CIRD by using nasal swabs.
    No preview · Article · Sep 2012 · Journal of Veterinary Medical Science
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    ABSTRACT: To investigate the potential transmission of subtype H3 influenza virus to cats, a serological survey was carried out in South Korea. Serum samples (n = 1027) were obtained from 809 pet cats and 218 domesticated cats living in urban colonies (D-cats) from 2008 to 2010, and tested using an influenza anti-nucleoprotein (NP)-specific enzyme-linked immunosorbent assay (ELISA) and the haemagglutination inhibition (HI) test, which was recommended by the World Organization for Animal Health. Anti-influenza virus antibodies were detected in 3.12% and 2.43% of cat sera tested using the NP-specific ELISA and HI test, respectively. Anti-H3 antibodies were also identified when the HI assay was used for influenza virus serotyping. These data may indicate the sporadic transmission of subtype H3 influenza virus from other infected species to cats in South Korea.
    No preview · Article · Jul 2012
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    ABSTRACT: Decursin and related coumarin compounds in herbal extracts have a number of biological activities against inflammation, angiogenesis and cancer. We have analysed a derivative of decursin (CSL-32) for activity against inflammatory activation of cancer cells, such as migration, invasion and expression of pro-inflammatory mediators. The human fibrosarcoma cell line, HT1080, was treated with TNFα (tumour necrosis factor α) in the presence or absence of CSL-32. The cellular responses and modification of signalling adapters were analysed with respect to the production of pro-inflammatory mediators, as also migration, adhesion and invasion. Treatment of HT1080 cells with CSL-32 inhibited their proliferation, without affecting cell viability, and TNFα-induced expression of pro-inflammatory mediators, such as MMP-9 (matrix metalloproteinase-9) and IL-8 (interleukin-8). CSL-32 also suppressed phosphorylation and degradation of IκB (inhibitory κB), phosphorylation of p65 subunit of NF-κB (nuclear factor-κB) and nuclear translocation of NF-κB, which are required for the expression of pro-inflammatory mediators. In addition, CSL-32 inhibited invasion and migration of HT1080 cells, as also cellular adhesion to fibronectin, an ECM (extracellular matrix) protein. CSL-32 treatment resulted in a dose-dependent inhibition of PI3K (phosphoinositide 3-kinase) activity, required for the cellular migration. The analyses show that CSL-32 inhibits processes associated with inflammation, such as the production of pro-inflammatory mediators, as well as adhesion, migration and invasion in HT1080 cells.
    No preview · Article · Jul 2012 · Cell Biology International

Publication Stats

2k Citations
282.75 Total Impact Points


  • 2004-2015
    • Kyungpook National University
      • • School of Food Science and Biotechnology
      • • College of Natural Sciences
      Daikyū, Daegu, South Korea
  • 2012
    • Konyang University
      • College of Medicine
      Ronsan, South Chungcheong, South Korea
  • 2002
    • Sungkyunkwan University
      • Samsung Medical Center
      Sŏul, Seoul, South Korea