Neuroprotective activity of chemokines against N-methyl-D-aspartate or beta-amyloid-induced toxicity in culture.
We have examined the effect of various chemokines on neuronal toxicity in culture. In mixed cortical cultures, challenged with a brief pulse of N-methyl-D-aspartate (NMDA, 60 microM, 10 min), chemokines were either present for 2 h preceding the pulse or they were co-applied with NMDA and then kept in the medium for the following 20-24 h. Interleukin-8 (IL-8), regulated on activation of normal T cells expressed and secreted (RANTES) and macrophage/monocyte chemoattractant protein-1 (MCP-1), were neuroprotective under both conditions, whereas stromal cell-derived factor 1alpha (SDF-1alpha) was protective only when applied during and after the NMDA pulse. Mixed or pure neuronal cultures were also exposed for 48 h to a toxic fragment of the beta-amyloid peptide (beta-amyloid peptide-(25-35), 12.5 or 25 microM) in the absence or presence of chemokines. Among a number of chemokines, only RANTES was neuroprotective against beta-amyloid peptide-(25-35)-induced neurotoxicity in both cultures. We conclude that activation of chemokine receptors differentially affects neuronal degeneration induced by excitotoxins or beta-amyloid peptide in cortical cultures.
Bruno
V
V
I.N.M. Neuromed, Pozzilli, Italy.
Copani
A
A
Besong
G
G
Scoto
G
G
Nicoletti
F
F
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000494:pharmacology; D018925:Chemokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D016209:Interleukin-8 / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D018946:Chemokine CCL5; D018925:Chemokines; D016209:Interleukin-8; D018696:Neuroprotective Agents; D016202:N-Methylaspartate