Title: Inflammatory Neurodegeneration Induced by Lipoteichoic Acid from Staphylococcus Aureus is Mediated by Glia Activation, Nitrosative and Oxidative Stress, and Caspase Activation
Authors: KINSNER AGNIESZKAPILOTTO ValentinaDEININGER SusanneBROWN Guy C.COECKE SANDRAHARTUNG THOMASPRICE ANNA
Citation: JOURNAL OF NEUROCHEMISTRY vol. 95 p. 1132-1143
Publisher: BLACKWELL PUBLISHING
Publication Year: 2005
JRC N°: JRC35006
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC35006
Type: Articles in Journals
Abstract: In this study we investigated the mechanisms of neuronal cell death induced by lipoteichoic acid (LTA) and muramyl dipeptide (MDP) from Gram-positive bacterial cell walls using primary cultures of rat cerebellum granule cells (CGCs) and rat cortical glial cells (astrocytes and microglia). LTA (+/- MDP) from Staphylococcus aureus induced strong inflammatory response of both types of glial cells (release of IL-1 beta, TNF-alpha and nitric oxide). The death of CGCs was caused by activated glia as in the absence of glia (treatment with 7.5 μM cytosine-D-arabinoside to inhibit non-neuronal cell proliferation) LTA + MDP did not cause significant cell death (less then 20%). Additionally, staining with rhodamine-labelled LTA confirmed that LTA was bound only to microglia and astrocytes (not neurons). Neuronal cell death induced by LTA (+/- MDP)-activated glia was partially blocked by an iNOS inhibitor (1400W, 100 μM), and completely blocked by a superoxide dismutase mimetic (MnTBAP, 50 μM) and a peroxynitrite scavenger (FeTPPS, 100 μM) suggesting that nitric oxide and peroxynitrite contributed to LTA-induced cell death. Moreover, neuronal cell death was inhibited by selective inhibitors of caspase-3 (z-DEVD-fmk, 50 μM) and caspase-8 (z-IETD-fmk, 50 μM) indicating that they were involved in LTA-induced neuronal cell death.
JRC Institute:Institute for Health and Consumer Protection

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