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Selective inflammatory stimulations enhance release of microglial response factor (MRF)‐1 from cultured microglia
Author(s) -
Tanaka Shuuitsu,
Koike Tatsuro
Publication year - 2002
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10142
Subject(s) - microglia , glutamate receptor , biology , agonist , microbiology and biotechnology , neuroglia , biophysics , receptor , biochemistry , neuroscience , central nervous system , inflammation , immunology
Abstract The mrf‐1 gene has been isolated from microglia exposed to cultured cerebellar granule neurons undergoing apoptosis. We have shown that mrf‐1 is upregulated in response to neuronal death and degeneration both in vitro and in vivo. However, the exact role of MRF‐1 remains unknown. Here we show that MRF‐1 is released from cultured rat microglia, and its release is greatly enhanced under inflammatory conditions. When microglia were treated with ATP, the amount of MRF‐1 that was released increased 10‐fold compared to the basal level of release. Enhanced MRF‐1 release was induced within 10 min and peaked within 1 h; after ∼ 4 h, the MRF‐1 release had returned to normal. MRF‐1 release was stimulated by 2‐methyl‐thio‐ATP (five‐fold) and a P2X 7 selective agonist, 2′‐ and 3′‐ O ‐(4‐benzoylbenzoyl)‐ATP (ten‐fold). Moreover, the ATP‐stimulated MRF‐1 release was inhibited by a P2X 7 selective antagonist, oxidized ATP (oATP), and also under a Ca 2+ ‐free condition. These results indicate that the effects of ATP are dependent on Ca 2+ influx through P2X 7 receptors. MRF‐1 release was enhanced by Ca 2+ ‐ionophore A23187 (sixfold), thapsigargin (threefold); however, it was not enhanced by glutamate or lipopolysaccharide. Moreover, a platelet‐activating factor enhanced microglial MRF‐1 release in a dose‐dependent manner. We also showed that a conditioned medium from cerebellar granule neurons undergoing apoptosis markedly increased MRF‐1 release from microglia; that effect was significantly inhibited by oATP. These results indicate that selective inflammatory stimulations, including ATP and PAF, enhance MRF‐1 release from microglia through a Ca 2+ ‐dependent mechanism and suggest that MRF‐1 may play a role in cell‐cell interactions under inflammatory conditions. GLIA 40:360–371, 2002. © 2002 Wiley‐Liss, Inc.