Detoxified lipopolysaccharide reduces microglial cell killing of prion-infected neurons.
In vitro studies show that microglial cells kill neurons treated with the synthetic miniprion (sPrP106) or with amyloid-beta1-42 (a neurotoxic peptide found in Alzheimer's disease) by a process requiring the CD14 protein. The killing of treated primary cortical neurons by microglial cells was reduced by the addition of detoxified lipopolysaccharide (LPS), a deacylated form of LPS. Detoxified LPS also increased the survival of prion-infected neuroblastoma cells incubated with microglial cells. The presence of detoxified LPS reduced cytokine production in these co-cultures, and from isolated microglial cells incubated with native LPS, or fibrils of sPrP106 or amyloid-beta1-42. These results suggest that some compounds that bind to CD14 might reduce microglial cell activation and increase neuronal survival in prion and Alzheimer's diseases.
Bate
Clive
C
Department of Veterinary Pathology, Glasgow University Veterinary School, Bearsden Road, Glasgow G61 1QH, UK. c.bate@vet.gla.ac.uk
Williams
Alun
A
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D008658:Inactivation, Metabolic; D007239:Infections / Q000628:therapy; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011328:Prions / Q000494:pharmacology*; D013778:Tetrazolium Salts
C110656:2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium; D016229:Amyloid beta-Peptides; D016207:Cytokines; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D010455:Peptides; D011328:Prions; D013778:Tetrazolium Salts; C078592:amyloid beta-protein (1-40)