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    Hypoxia/reoxygenation-mediated induction of astrocyte interleukin 6: a paracrine mechanism potentially enhancing neuron survival.

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    YanShirley_JEM_1994.pdf (2.084Mb)
    Issue Date
    1994-12-01
    Author
    Maeda, Yusuke
    Matsumoto, Masayasu
    Hori, Osamu
    Kuwabara, Keisuke
    Ogawa, Satoshi
    Yan, Shirley ShiDu
    Ohtsuki, Toshiho
    Kinoshita, Taroh
    Kamada, Takenobu
    Stern, David M.
    Publisher
    The Rockefeller University Press
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Metadata
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    Abstract
    To elucidate mechanisms underlying neuroprotective properties of astrocytes in brain ischemia, production of neurotrophic mediators was studied in astrocytes exposed to hypoxia/reoxygenation (H/R). Rat astrocytes subjected to H/R released increased amounts of interleukin (IL) 6 in a time-dependent manner, whereas levels of tumor necrosis factor and IL-1 remained undetectable. IL-6 transcripts were induced in hypoxia and the early phase of reoxygenation, whereas synthesis and release of IL-6 antigen/activity occurred during reoxygenation. Elevated levels of IL-6 mRNA were due, at least in part, to increased transcription, as shown by nuclear runoff analysis. The mechanism stimulating synthesis and release of IL-6 antigen by astrocytes was probably production of reactive oxygen intermediates (ROIs), which occurred within 15-20 minutes after placing hypoxia cultures back into normoxia, as the inhibitor diphenyl iodonium inhibited the burst of ROIs and subsequent IL-6 generation (blockade of nitric oxide formation had no effect on ROI generation or IL-6 production). Enhanced IL-6 generation was also observed in human astrocytoma cultures exposed to H/R. Survival of differentiated PC12 cells exposed to H/R was potentiated by conditioned medium from H/R astrocytes, an effect blocked by neutralizing anti-IL-6 antibody. In a gerbil model of brain ischemia, IL-6 activity was lower in the hippocampus, an area sensitive to ischemia, compared with IL-6 activity in the cortex, an area more resistant to ischemia. IL-6 antigen, demonstrated immunohistochemically, was increased in astrocytes from ischemic regions of gerbil brain. These data suggest that H/R enhances transcription of IL-6, resulting in increased translation and release of IL-6 antigen after the burst of ROI generated early during reoxygenation. Release of IL-6 from astrocytes could exert a paracrine neurotrophic effect in brain ischemia.
    Description
    This is the published version. Copyright 1994 The Rockefeller University Press.
    URI
    http://hdl.handle.net/1808/17862
    DOI
    https://doi.org/10.1084/jem.180.6.2297
    Collections
    • Pharmacy Scholarly Works [286]
    Citation
    Maeda, Y, M Matsumoto, O Hori, K Kuwabara, S Ogawa, S D Yan, T Ohtsuki, T Kinoshita, T Kamada, and D M Stern. "Hypoxia/reoxygenation-mediated Induction of Astrocyte Interleukin 6: A Paracrine Mechanism Potentially Enhancing Neuron Survival." Journal of Experimental Medicine 180.6 (1994): 2297-308. doi: 10.1084/jem.180.6.2297.

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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