Inflammatory neurodegeneration induced by lipoteichoic acid from Staphylococcus aureus is mediated by glia activation, nitrosative and oxidative stress, and caspase activation

Agnieszka Kinsner, Valentina Pilotto, Susanne Deininger, Guy C. Brown, Sandra Coecke, Thomas Hartung, Anna Bal-Price

Research output: Contribution to journalArticle

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 a strong inflammatory response of both types of glial cells (release of interleukin-1 β, tumour necrosis factor-α and nitric oxide). The death of CGCs was caused by activated glia because 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 than 20%). In addition, staining with rhodamine-labelled LTA confirmed that LTA was bound only to microglia and astrocytes (not neurones). Neuronal cell death induced by LTA (± MDP)-activated glia was partially blocked by an inducible nitric oxide synthase inhibitor (1400 W; 100 μM), and completely blocked by a superoxide dismutase mimetic [manganese (III) tetrakis (4-benzoic acid)porphyrin chloride; 50 μM] and a peroxynitrite scavenger [5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrinato iron (III); 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-lle-Glu(O-Me)-Thr-Asp(O-Me) fluoromethyl ketone; 50 μM) indicating that they were involved in LTA-induced neuronal cell death.

Original languageEnglish (US)
Pages (from-to)1132-1143
Number of pages12
JournalJournal of Neurochemistry
Volume95
Issue number4
DOIs
StatePublished - Nov 1 2005
Externally publishedYes

Keywords

  • Gram-positive bacteria
  • Inflammation
  • Neurotoxicity
  • Reactive oxygen and nitrogen species

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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