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C6 glioma cell insoluble matrix components enhance interferon-gamma-stimulated inducible nitric-oxide synthase/nitric oxide production in BV2 microglial cells.

Abstract

Microglia are the primary central nervous system immune effector cells. Microglial activation is linked to interactions with extracellular cytokines and the extracellular matrix (ECM). Astrocytomas are characterized by their diffuse nature, which is regulated by insoluble ECM components produced by the tumor cells that are largely absent from normal central nervous system tissue. The present study examined the influence of astrocytoma (C6 rat glioma) insoluble matrix components on interferon-gamma (IFN-gamma)-mediated inducible nitric-oxide synthase (iNOS) induction in microglial cells. We found that IFN-gamma-stimulated iNOS induction and nitric oxide release was greater in microglia cultured on C6 glioma cell-derived matrices compared with microglia cultured on primary rat astrocyte-derived matrices. Culture of microglia on C6 glioma cell-derived matrices also led to activation of STAT1, augmentation of IFN-gamma-induced STAT-3 activation, and an increase in IFN-gamma-activated site (GAS)-luciferase reporter activity. In addition, culture of microglia on C6 glioma cell-derived matrices activated NF-kappaB DNA binding activity and transcriptional activity. The results suggest that insoluble matrix components derived from malignant glioma cells can regulate microglia activation. These factors may include ECM components, such as fibronectin, collagen, laminin, vitronectin, and other nondiffusible compounds, and laminin seems to a critical regulator of this process. Microglia activation and subsequent brain inflammation may influence tumor growth, treatment, and metastasis. Better understanding of the regulation of microglial activation by astrocytoma-derived insoluble matrix components may be important in the development of immune-based treatment strategies against malignant brain tumors.

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  • Authors+Show Affiliations

    ,

    Department of Physiology and Biophysics, Inha University, College of Medicine, 253 Yonghyun-Dong, Nam-Ku, Incheon, Republic of Korea.

    , , , ,

    Source

    The Journal of biological chemistry 283:5 2008 Feb 01 pg 2526-33

    MeSH

    Animals
    Base Sequence
    Cell Adhesion
    Cell Line
    Cell Line, Tumor
    Cell Movement
    Coculture Techniques
    DNA Primers
    Enzyme Induction
    Extracellular Matrix
    Glioma
    Interferon-gamma
    Mice
    Microglia
    Nitric Oxide
    Nitric Oxide Synthase Type II
    RNA, Messenger
    Rats
    Recombinant Proteins
    STAT1 Transcription Factor
    STAT3 Transcription Factor

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17981810

    Citation

    Kim, Yoon-Jung, et al. "C6 Glioma Cell Insoluble Matrix Components Enhance Interferon-gamma-stimulated Inducible Nitric-oxide Synthase/nitric Oxide Production in BV2 Microglial Cells." The Journal of Biological Chemistry, vol. 283, no. 5, 2008, pp. 2526-33.
    Kim YJ, Hwang SY, Hwang JS, et al. C6 glioma cell insoluble matrix components enhance interferon-gamma-stimulated inducible nitric-oxide synthase/nitric oxide production in BV2 microglial cells. J Biol Chem. 2008;283(5):2526-33.
    Kim, Y. J., Hwang, S. Y., Hwang, J. S., Lee, J. W., Oh, E. S., & Han, I. O. (2008). C6 glioma cell insoluble matrix components enhance interferon-gamma-stimulated inducible nitric-oxide synthase/nitric oxide production in BV2 microglial cells. The Journal of Biological Chemistry, 283(5), pp. 2526-33.
    Kim YJ, et al. C6 Glioma Cell Insoluble Matrix Components Enhance Interferon-gamma-stimulated Inducible Nitric-oxide Synthase/nitric Oxide Production in BV2 Microglial Cells. J Biol Chem. 2008 Feb 1;283(5):2526-33. PubMed PMID: 17981810.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - C6 glioma cell insoluble matrix components enhance interferon-gamma-stimulated inducible nitric-oxide synthase/nitric oxide production in BV2 microglial cells. AU - Kim,Yoon-Jung, AU - Hwang,So-Young, AU - Hwang,Ji-Sun, AU - Lee,Jung-Weon, AU - Oh,Eok-Soo, AU - Han,Inn-Oc, Y1 - 2007/11/02/ PY - 2007/11/6/pubmed PY - 2008/4/3/medline PY - 2007/11/6/entrez SP - 2526 EP - 33 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 283 IS - 5 N2 - Microglia are the primary central nervous system immune effector cells. Microglial activation is linked to interactions with extracellular cytokines and the extracellular matrix (ECM). Astrocytomas are characterized by their diffuse nature, which is regulated by insoluble ECM components produced by the tumor cells that are largely absent from normal central nervous system tissue. The present study examined the influence of astrocytoma (C6 rat glioma) insoluble matrix components on interferon-gamma (IFN-gamma)-mediated inducible nitric-oxide synthase (iNOS) induction in microglial cells. We found that IFN-gamma-stimulated iNOS induction and nitric oxide release was greater in microglia cultured on C6 glioma cell-derived matrices compared with microglia cultured on primary rat astrocyte-derived matrices. Culture of microglia on C6 glioma cell-derived matrices also led to activation of STAT1, augmentation of IFN-gamma-induced STAT-3 activation, and an increase in IFN-gamma-activated site (GAS)-luciferase reporter activity. In addition, culture of microglia on C6 glioma cell-derived matrices activated NF-kappaB DNA binding activity and transcriptional activity. The results suggest that insoluble matrix components derived from malignant glioma cells can regulate microglia activation. These factors may include ECM components, such as fibronectin, collagen, laminin, vitronectin, and other nondiffusible compounds, and laminin seems to a critical regulator of this process. Microglia activation and subsequent brain inflammation may influence tumor growth, treatment, and metastasis. Better understanding of the regulation of microglial activation by astrocytoma-derived insoluble matrix components may be important in the development of immune-based treatment strategies against malignant brain tumors. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/17981810/C6_glioma_cell_insoluble_matrix_components_enhance_interferon_gamma_stimulated_inducible_nitric_oxide_synthase/nitric_oxide_production_in_BV2_microglial_cells_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=17981810 DB - PRIME DP - Unbound Medicine ER -