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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| Published in: | Journal of neuroimmunology Vol. 166; no. 1; pp. 113 - 125 |
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| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
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Elsevier B.V
01-09-2005
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| Abstract | 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. |
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| AbstractList | 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. |
| Author | Watters, Jyoti J. Frasier, Chuenchanok Nikodemova, Maria Brautigam, Vielska M. |
| Author_xml | – sequence: 1 givenname: Vielska M. surname: Brautigam fullname: Brautigam, Vielska M. organization: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, United States – sequence: 2 givenname: Chuenchanok surname: Frasier fullname: Frasier, Chuenchanok organization: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, United States – sequence: 3 givenname: Maria surname: Nikodemova fullname: Nikodemova, Maria organization: Department of Medical Sciences, University of Wisconsin, Madison, WI 53706, United States – sequence: 4 givenname: Jyoti J. surname: Watters fullname: Watters, Jyoti J. email: jjwatters@wisc.edu organization: Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, United States |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/15979729$$D View this record in MEDLINE/PubMed |
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| Keywords | Signal transduction Phosphorylation Inflammation Cyclooxygenase-2 ATP Nitric oxide |
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| SubjectTerms | 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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