Mitogen-activated protein kinases activated by lipopolysaccharide and beta-amyloid in cultured rat microglia.
To test whether mitogen-activated protein kinases (MAPKs) are involved in microglial activation, pure microglia prepared from 1- to 3-day-old rat brains were activated with either 100 ng/ml lipopolysaccharide (LPS) or 5 nM synthetic beta-amyloid (Abeta) (25-35). The patterns of MAPK activation following LPS and Abeta treatment were very similar. Three MAPK subtypes, p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) were activated within 15 min and the activities of p38 and ERK were rapidly reduced to background level within 30 min while that of JNK was maintained for over 1 h. Both inhibitors of p38 (SB203580) and ERK pathway (PD098059) reduced LPS-induced nitric oxide (NO) release and Abeta-induced tumor necrosis factor-alpha (TNF-alpha) release. Furthermore, co-treatment of SB203580 and PD098059 additively reduced NO and TNF-alpha release. These results suggest that MAPK, at least p38 and ERK, mediate LPS-, and Abeta-induced microglial activation.
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Department of Pharmacology, Ajou University School of Medicine, Korea.
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D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000009:adverse effects / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000009:adverse effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects / Q000201:enzymology*; D008934:Mitogens / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012477:Salmonella enteritidis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016229:Amyloid beta-Peptides; D005419:Flavonoids; D007093:Imidazoles; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008934:Mitogens; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one