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,