title: Lipoteichoic acid induces prostaglandin E(2) release and cyclooxygenase-2 synthesis in rat cortical neuronal cells: involvement of PKCepsilon and ERK activation.
abstract: Inflammatory processes occur in the central nervous system (CNS) through mechanisms that differ from other inflammation, and with distinct cellular effects. Neuronal injury in bacterial meningitis is not a monocausal event, but is mediated by several factors. One is possible direct toxicity of bacterial compounds. Lipoteichoic acid (LTA) is a cell wall component unique to Gram-positive bacteria. In a previous report, LTA could interact with CD14 to induce NF-kappaB activation, which is involved in transcriptional regulation of adhesion molecules, enzymes and cytokines. Although there are many aspects to neuroinflammation, the pathways involving the cyclooxygenase (COX)-2 and subsequent generation of prostaglandin clearly play a role. LTA has been shown to stimulate inflammatory responses in a number of in vivo and in vitro experimental models. However, little was known about the molecular mechanisms of LTA implicated in inflammatory responses in neurons. In this study, we characterized the mechanisms underlying signaling transduction in rat cortical neuronal cells challenged by LTA. Here, we first showed that in rat cortical neuronal cells, LTA might activate protein tyrosine kinase (PTK), phosphatidylcholine-specific phospholipase C (PC-PLC), and phosphatidylinositol-specific phospholipase C (PI-PLC) to induce protein kinase Cepsilon activation, which in turn induces extracellular signal-regulated kinase (ERK) activation, finally inducing PGE(2) release and COX-2 synthesis.
authors.affiliation: Department of Medical Technology, Taipei Medical University, No 250. Wu-Hsing St. Taipei 110, Taiwan. wuhh@tmu.edu.tw
authors.forename: Hsueh-Hsia
authors.initials: HH
authors.lastname: Wu
authors.forename: Wen-Shyang
authors.initials: WS
authors.lastname: Hsieh
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Yang
authors.forename: Ming-Chuan
authors.initials: MC
authors.lastname: Tsai
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000096:biosynthesis*; D015232:Dinoprostone / Q000032:analysis / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D013682:Teichoic Acids / Q000633:toxicity*
chemical_list: D007527:Isoenzymes; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D013682:Teichoic Acids; C009900:lipoteichoic acid; D051546:Cyclooxygenase 2; D051744:Protein Kinase C-epsilon; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone