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Hypoxia/reoxygenation-mediated induction of astrocyte interleukin 6: a paracrine mechanism potentially enhancing neuron survival.
dc.contributor.author | Maeda, Yusuke | |
dc.contributor.author | Matsumoto, Masayasu | |
dc.contributor.author | Hori, Osamu | |
dc.contributor.author | Kuwabara, Keisuke | |
dc.contributor.author | Ogawa, Satoshi | |
dc.contributor.author | Yan, Shirley ShiDu | |
dc.contributor.author | Ohtsuki, Toshiho | |
dc.contributor.author | Kinoshita, Taroh | |
dc.contributor.author | Kamada, Takenobu | |
dc.contributor.author | Stern, David M. | |
dc.date.accessioned | 2015-05-28T14:59:40Z | |
dc.date.available | 2015-05-28T14:59:40Z | |
dc.date.issued | 1994-12-01 | |
dc.identifier.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. | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/17862 | |
dc.description | This is the published version. Copyright 1994 The Rockefeller University Press. | en_US |
dc.description.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. | en_US |
dc.publisher | The Rockefeller University Press | en_US |
dc.title | Hypoxia/reoxygenation-mediated induction of astrocyte interleukin 6: a paracrine mechanism potentially enhancing neuron survival. | en_US |
dc.type | Article | |
kusw.kuauthor | Yan, Shirley ShiDu | |
kusw.kudepartment | Pharmacology & Toxicology | en_US |
dc.identifier.doi | 10.1084/jem.180.6.2297 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item does not meet KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |
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