Purinergic receptor modulation of BV-2 microglial cell activity: Potential involvement of p38 MAP kinase and CREB

ATP is abundant in the extracellular fluid following brain injury, and it exerts potent modulatory effects on microglia, whose hyperactivation is thought to exacerbate neuronal damage. We show here that ATP decreases LPS-stimulated iNOS and COX-2 expression and reduces NO release in BV-2 microglia b...

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Veröffentlicht in:Journal of neuroimmunology 2005-09, Vol.166 (1), p.113-125
Hauptverfasser: Brautigam, Vielska M., Frasier, Chuenchanok, Nikodemova, Maria, Watters, Jyoti J.
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container_end_page 125
container_issue 1
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container_title Journal of neuroimmunology
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creator Brautigam, Vielska M.
Frasier, Chuenchanok
Nikodemova, Maria
Watters, Jyoti J.
description ATP is abundant in the extracellular fluid following brain injury, and it exerts potent modulatory effects on microglia, whose hyperactivation is thought to exacerbate neuronal damage. We show here that ATP decreases LPS-stimulated iNOS and COX-2 expression and reduces NO release in BV-2 microglia by a mechanism involving p38 MAP kinase. Further, we demonstrate that the inhibitory effects of ATP on NO production occur within 30 min of exposure and correlate with activation of the transcription factor CREB. Together, these data suggest that ATP may exert neuroprotective effects in the brain via a mechanism involving augmented activation of the p38/CREB pathway.
doi_str_mv 10.1016/j.jneuroim.2005.05.012
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subjects Adenine Nucleotides - metabolism
Adenosine Triphosphate - pharmacology
Animals
ATP
Cell Line
Cell Survival
Cyclic AMP Response Element-Binding Protein - metabolism
Cyclic AMP Response Element-Binding Protein - physiology
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors - pharmacology
Enzyme Inhibitors - pharmacology
Imidazoles - pharmacology
Inflammation
Inflammation Mediators - antagonists & inhibitors
Lipopolysaccharides - pharmacology
Mice
Microglia - metabolism
Microglia - physiology
Nitric oxide
Nitric Oxide - antagonists & inhibitors
Nitric Oxide - metabolism
Nitric Oxide Synthase - antagonists & inhibitors
Nitric Oxide Synthase - metabolism
Nitric Oxide Synthase Type II
p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases - physiology
Phosphorylation
Phosphorylation - drug effects
Prostaglandin-Endoperoxide Synthases - metabolism
Pyridines - pharmacology
Receptors, Purinergic - physiology
Receptors, Purinergic P2 - metabolism
Receptors, Purinergic P2 - physiology
Receptors, Purinergic P2X7
Signal transduction
Time Factors
title Purinergic receptor modulation of BV-2 microglial cell activity: Potential involvement of p38 MAP kinase and CREB
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