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 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.
Department of Comparative Biosciences, University of Wisconsin, Madison, WI 53706, USA.
Vielska M
VM
Brautigam
Chuenchanok
C
Frasier
Maria
M
Nikodemova
Jyoti J
JJ
Watters
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism / Q000502:physiology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010766:Phosphorylation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000502:physiology*; D018048:Receptors, Purinergic P2 / Q000378:metabolism / Q000502:physiology; D058486:Receptors, Purinergic P2X7; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D000227:Adenine Nucleotides; D017362:Cyclic AMP Response Element-Binding Protein; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C546469:P2rx7 protein, mouse; D011725:Pyridines; D011983:Receptors, Purinergic; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580