Stimulus-dependent requirement of ion channels for microglial NADPH oxidase-mediated production of reactive oxygen species.
Reactive oxygen species (ROS) produced by activated microglial cells play a pivotal role in the pathogenesis of neuro-degenerative and neuro-inflammatory diseases. Here we demonstrate that the pro-inflammatory lipid lysophosphatidylcholine (LPC) is capable of inducing microglial ROS production, which is mediated by the activity of NADPH oxidase. Inhibition of TRPV1 non-selective cation channels abolished ROS production in LPC-stimulated microglia, whereas inhibitors of K(+) channels, H(+) channels and Cl(-) channels had no significant effects. In contrast, activity of all four ion channel types was required for PMA-induced NADPH oxidase-mediated ROS generation, suggesting a differential, stimulus-dependent regulation of microglial ROS production by ion channel activity.
Schilling
Tom
T
Division of Basic Medical Sciences, St. George's, University of London, London, United Kingdom.
Eder
Claudia
C
D000818:Animals; D002461:Cell Line, Transformed; D004224:Diterpenes / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007202:Indicators and Reagents / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012430:Ruthenium Red / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004224:Diterpenes; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D010703:Phorbol Esters; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; C468130:iodoresiniferatoxin; D012430:Ruthenium Red; C008874:phorbol-12,13-diacetate; D019255:NADPH Oxidases