title: Control of JNK for an activation of NADPH oxidase in LPS-stimulated BV2 microglia.
abstract: NADPH oxidase is a main regulator for H(2)O(2) productivity in neuroinflammatory cells, including microglia, under various CNS diseases and its activity is controlled by mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase (JNK). However, little is known about the link between NADPH oxidase-driven H(2)O(2) productivity and JNK in microglia. The purpose of this study is to uncover the link using lipopolysaccharide (LPS)-stimulated BV2 microglia. LPS-stimulated BV2 microglia produced H(2)O(2) that was decreased by NADPH oxidase inhibitors, including 4-(2-aminoethyl)benzenesulfonylfluoride and diphenyleneiodonium chloride. In addition, NADPH oxidase was activated in LPS-stimulated BV2 cells. These results suggest that NAPDH oxidase is a main factor for H(2)O(2) productivity in LPS-stimulated BV2 microglia. Based on a semi-quantitative PCR analysis, two of NADPH oxidase components, p47(phox) and gp91(phox), were involved in the activation of NADPH oxidase because transcriptional levels of both components were upregulated by LPS. Role of JNK in NADPH oxidase-regulated H(2)O(2) productivity was pursued using specific inhibitors, including SP600125 and JNK inhibitory peptide (JIP). Inhibition of the JNK pathways significantly reduced H(2)O(2) productivity, which was closely related to the attenuation of NADPH oxidase activation and the upregulation of components. We conclude that JNK pathways are involved in NADPH oxidase-mediated H(2)O(2) productivity in BV2 microglia.
authors.affiliation: Department of Pharmacology, College of Pharmacy, Gachon University of Medicine and Science, Incheon, 406-799, Korea.
authors.forename: Jung Eun
authors.initials: JE
authors.lastname: Han
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology; D018613:Microscopy, Confocal; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases; D048031:JNK Mitogen-Activated Protein Kinases