p38 mitogen-activated protein kinase mediates lipopolysaccharide, not interferon-gamma, -induced inducible nitric oxide synthase expression in mouse BV2 microglial cells.
The present study examined the role of mitogen - activated protein kinases (MAPKs) in inducible nitric oxide synthase (iNOS) induction by lipopolysaccharide (LPS) or interferon - gamma (IFN - gamma) in the murine microglial cell line BV2 cells. LPS rapidly (<2 h) induced iNOS mRNA expression whereas IFN - gamma did not within 8 h after stimulation. LPS activated three MAPK subtypes, extracellular signal - regulated kinase (ERK), p38 and c - Jun N - terminal kinase (JNK) as early as 15 min after stimulation. In contrast, IFN - gamma activated only ERK after 6 h of stimulation and did not alter the activity of p38 and JNK. LPS-induced iNOS expression was markedly decreased by the p38 inhibitor SB203580, but not by the MAPK or ERK kinase inhibitor PD98059. IFN - gamma - induced nitric oxide (NO) generation was partially inhibited by PD98059 and SB203580 only in combination. The results demonstrate that MAPKs differentially mediate NO production by LPS - and IFN - gamma in BV2 cells.
Han
Inn Oc
IO
Department of Pharmacology, College of Medicine, Ewha Institute of Neuroscience, Ewha Women's University, 70 Chongro-6-ga, Chongro-ku, Seoul 110-783, South Korea.
Kim
Ki-Wan
KW
Ryu
Jong Hoon
JH
Kim
Won-Ki
WK
D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D008070:Lipopolysaccharides; D011725:Pyridines; D012333:RNA, Messenger; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one