Functional polarization of neuroglia: Implications in neuroinflammation and neurological disorders

Jha, M.K.,Lee, W.H.,Suk, K. Pergamon Press 2016 Biochemical pharmacology Vol.103 No.-

<P>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. (C) 2015 Elsevier Inc. All rights reserved.</P>

Highly Porous Silica Nanoaerogels for Ultrafast Nonlinear Optical Applications

Seo, Jae Tae,Ma, S.M.,Lee, K.,Brown, H.,Jackson, A.,Skyles, T.,Cubbage, N.M.,Tabibi, B.,Yoo, K.P.,Kim, Suk Young,Jung, S.S.,Namkung, M. Trans Tech Publications, Ltd. 2005 Key Engineering Materials Vol.287 No.-

<P>Highly porous silica nanoaerogels with low apparent density of ~0.1 g/cm3 and ~0.07 g/cm3 were synthesized through two-step sol-gel processing and low temperature supercritical fluid drying. The nonlinear refraction (γ) of silica nanoaerogels was estimated to be ~ -3.4 x 10-16 m2/W for ~0.1 g/cm3 and ~0.07 g/cm3 apparent densities with a signal-beam femtosecond z-scan spectroscopy. The third-order nonlinear refraction coefficient of nanostructure silica nanoaerogels was almost four orders larger than that of bulk silica materials. The large nonlinearrefraction with high nonlinear figure of merit (γ/βλ, β~2×10-10 m/W for 0.07 g/cm3 apparent density, β~6×10-10 m/W for 0.1 g/cm3 apparent density, λ~0.775 µm) is an ideal optical property for nonlinear applications of homeland security, battlefield enhancement, and industrial uses.</P>

A novel small-molecule agonist of PPAR-γ potentiates an anti-inflammatory M2 glial phenotype

Song, G.J.,Nam, Y.,Jo, M.,Jung, M.,Koo, J.Y.,Cho, W.,Koh, M.,Park, S.B.,Suk, K. Pergamon Press 2016 NEUROPHARMACOLOGY - Vol.109 No.-

Neuroinflammation is a key process for many neurodegenerative diseases. Activated microglia and astrocytes play an essential role in neuroinflammation by producing nitric oxide (NO), inflammatory cytokines, chemokines, and neurotoxins. Therefore, targeting glia-mediated neuroinflammation using small-molecules is a potential therapeutic strategy. In this study, we performed a phenotypic screen using microglia cell-based assay to identify a hit compound containing N-carbamoylated urethane moiety (SNU-BP), which inhibits lipopolysaccharide (LPS)-induced NO production in microglia. SNU-BP inhibited pro-inflammatory cytokines and inducible nitric oxide synthase in LPS-stimulated microglia, and potentiated interleukin-4-induced arginase-1 expression. PPAR-γ was identified as a molecular target of SNU-BP. The PPAR response element reporter assay revealed that SNU-BP specifically activated PPAR-γ, but not PPAR-δ or -α, confirming that PPAR-γ is the target protein of SNU-BP. The anti-inflammatory effect of SNU-BP was attenuated by genetic and pharmacological inhibition of PPAR-γ. In addition, SNU-BP induced an anti-inflammatory phenotype in astrocytes as well, by inhibiting pro-inflammatory NO and TNF-α, while increasing anti-inflammatory genes, such as arginase-1 and Ym-1. Finally, SNU-BP exhibited an anti-inflammatory effect in the LPS-injected mouse brain, demonstrating a protective potential for neuroinflammatory diseases.

Glucose Sensor Based on Glucose Oxidase-Lipid LB Film Immobilized in Prussian Blue Layer

Lee, Dong-Yun,Kafi, A. K. M.,Choi, Won-Suk,Park, Sang-Hyun,Kwon, Young-Soo American Scientific Publishers 2008 Journal of Nanoscience and Nanotechnology Vol.8 No.9

<P>The structure and dynamic organization of a mixed Langmuir film of glucose oxidase (GOx) and lipid at the air-water interface were studied. The film was transferred onto the Prussian Blue (PB)-modified Pt electrode for biosensor preparation. The PB modified electrode showed well defined redox peaks in 0.1 M PBS electrolyte. The Langmuir film was characterized at the air-water interface by <I>π</I>-A isotherms. The mixed monolayer was formed by spreading GOx on the LB trough covered with lipid. Time-pressure results show that at least 90 minutes are required to reach the equilibrium state of GOx-lipid film. The monolayer was transferred onto the PB-modified electrode when surface pressure was 40 mN/m. This sensor was characterized by a very low detection limit and a wide linear range. The optimal conditions for both fabricating and response of the sensor were investigated. The proposed biosensor showed a linear calibration range from 5 × 10<SUP>−6</SUP> to 6 × 10<SUP>−5</SUP> M. The detection limit was determined to be 1.5 × 10<SUP>−6</SUP> M.</P>

Immobilization, Hybridization and Amperometric Detection of DNA Sensor Using Quartz Crystal Microbalance

Lee, Dong-Yun,Choi, Won-Suk,Kafi, A. K. M.,Park, Sang-Hyun,Kwon, Young-Soo American Scientific Publishers 2008 Journal of Nanoscience and Nanotechnology Vol.8 No.9

<P>A synthesized 21-mer single-stranded DNA (ssDNA) was covalently immobilized onto a self-assembled aminoethanethiol monolayer modified gold electrode onto quartz crystal microbalance (QCM). The covalently immobilized ssDNA was hybridized with complementary ssDNA. The interaction between surface-immobilized ssDNA and complementary 21-mer DNA in solution was also examined. Each step was followed by monitoring changes in the QCM frequency over time. From the results, the measured frequency change was about 256 Hz, 160 Hz and 141 Hz, respectively. As a result, the adsorption mass was about 273 ng/cm<SUP>2</SUP>, 171 ng/cm<SUP>2</SUP> and 151 ng/cm<SUP>2</SUP>, according to the Sauerbrey equation. Also, PBS with pH 7.0 was selected as a supporting electrolyte to achieve maximum sensitivity and good bioactivity. The anodic peak current was linearly related to the concentrations between 1 × 10<SUP>−5</SUP> and 9 × 10<SUP>−5</SUP> M with a detection limit of 1.0 × 10 <SUP>−6</SUP> M.</P>

IFNγ/TNFα synergism as the final effector in autoimmune diabetes : A key role for IRF-1 in β-cell death

Suk, K,Kim, S,Kim, YH,Kim, K-A,Yagita H,Kayagaki N,Shong, M,Lee, M-S 이화여자대학교 세포신호전달연구센터 2000 고사리 세포신호전달 심포지움 Vol. No.2

T cell-mediated apoptosis is responsible for pancreatic β-islet cell death in autoimmune diabetes of NOD mice. Perforin, TNFα, FasL and IL-1 have been considered as effector molecule(s) leading to β-cell death, however, real culprit(s) in β-cell destruction have long been elusive despite intense investigation. Our previous studies demonstrated that FasL is not an effector in this process(1, 2), contrary to previous reports(3, 4). In the current work, we attempted to identify the final effector molecule(s) in β-cell death of autoimmune diabetes. The combination of IFNγ and TNFα, but not either cytokine alone, exerted a significant cytotoxicity on isolated islet cells as well as MIN6N8 cells, an SV40-transformed insulinoma cell line derived from NOD mice. IFNγ and TNFα synergistically induced MIN6N8 cell death by a caspase-dependent apoptosis. STAT-1 was activated by IFNγ followed by induction of IRF-1 and caspase-1, which rendered otherwise resistant islet cells susceptible to TNFα-mediated apoptosis. The β-cell death by IFNγ/TNFα was blocked by YVAD, a caspase-1-specific inhibitor. Transfection of IRF-1 cDNA sensitized MIN6N8 cells to TNFα-induced cytotoxicity, while phosphorylation-defective mutant of STAT1 abolished islet cell vulnerablity to IFNγ/TNFα. STAT1 and IRF-1 were up-regulated in pancreatic islet cells of diabetic NOD mice. Finally, anti-TNFα antibody significantly inhibited the development of diabetes after adoptive transfer of lymphocytes. Taken together, our results strongly indicated that IFNγ and TNFα synergistically act as the final effector molecules in autoimmune diabetes. Our data also suggest a novel mechanism of IFNγ/TNFα synergism: IFNγ renders otherwise resistant cells susceptible to TNFα-induced apoptosis through the induction of IRF-1. This cytokine synergism not only provides insight into the mechanism of islet destruction in autoimmune diabetes but also has relevance in other organ specific autoimmune diseases and anti-tumor effects of the cytokines where a similar cytokine synergism was reported.

구연 : 그랜드볼룸 ; 한국의 전향적-전국적인 독성 간질환 연구 (초)

( K. T. Suk ),( Y. O. Kweon ),( B. I. Kim ),( S. H. Kim ),( I. H. Kim ),( J. H. Kim ),( S. W. Nam ),( Y. H. Paik ),( J. I. Seo ),( J. H. Sohn ),( B. M. Ahn ),( S. H. Um ),( H. J. Lee ),( M. Cho ),( M. 대한간학회 2010 Clinical and Molecular Hepatology(대한간학회지) Vol.16 No.3(S)

Impact of Bacterial Translocation on Hepatopulmonary Syndrome: A Prospective Observational Study

Suk, K. T.,Kim, M. Y.,Jeong, S. W.,Jang, J. Y.,Jang, Y. O.,Baik, S. K. Springer Science + Business Media 2018 Digestive diseases and sciences Vol.63 No.1

<P>HPS is a common complication with a prevalence of 41.5% in patients with cirrhosis. Bacterial translocation and portal pulmonary vascular dilatation are key mechanism involved in the progression of HPS.</P>

Splenic volume can be a novel predictive parameter for the prognosis of chronic lymphocytic leukemia?

Song, M.-K.,Chung, J.-S.,Lee, H.-S.,Kim, S.-H.,Suk-Kim,,Yun, E.-Y.,Seol, Y.-M.,Shin, H.-J.,Choi, Y.-J.,Cho, G.-J. Elsevier 2010 ANNALS OF ONCOLOGY Vol.21 No.12

The pivotal role played by lipocalin-2 in chronic inflammatory pain

Jha, M.K.,Jeon, S.,Jin, M.,Ock, J.,Kim, J.H.,Lee, W.H.,Suk, K. Academic Press 2014 Experimental neurology Vol.254 No.-

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 12h 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 naive 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.