Inflammatory Neurodegeneration Induced by Lipoteichoic Acid from Staphylococcus Aureus is Mediated by Glia Activation, Nitrosative and Oxidative Stress, and Caspase Activation

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.

KINSNER Agnieszka;  PILOTTO Valentina;  DEININGER Susanne;  BROWN Guy C.;  COECKE Sandra;  HARTUNG Thomas;  PRICE Anna; 

2006-12-13

BLACKWELL PUBLISHING

JRC35006

https://publications.jrc.ec.europa.eu/repository/handle/JRC35006,