Endotoxin preconditioning protects neurones from in vitro ischemia: role of endogenous IL-1beta and TNF-alpha.
We have examined whether changes in the expression of several inflammatory factors mediate the neuroprotective action of LPS preconditioning on cerebellar granule neurones (CGN) exposed to the mitochondrial toxin 3-nitropropionic acid (3-NP), chosen as an in vitro ischemic model. CGN were either directly pre-treated with LPS or indirectly by exposure to conditioned medium (CM) from LPS-treated mixed glial cultures obtained from wild type or IL-1beta-knock out mice. Following this pre-treatment CGN were incubated with 3-NP and cell viability assessed. Our results show that LPS preconditioning in neurones, promotes neuronal survival against 3-NP-induced cell death and that endogenous TNF-alpha is a critical mediator for the neuroprotective actions of LPS independently of the presence of endogenous IL-1beta after 3-NP exposure.
Lastres-Becker
Isabel
I
Section Molecular Neurogenetics, Building 26, Room 509, J.W. Goethe Universität, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.
Cartmell
Tam
T
Molina-Holgado
Francisco
F
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003292:Convulsants / Q000633:toxicity; D017077:Culture Media, Conditioned; D004731:Endotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D007511:Ischemia / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009574:Nitro Compounds / Q000633:toxicity; D011422:Propionates / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D003292:Convulsants; D017077:Culture Media, Conditioned; D004731:Endotoxins; D007375:Interleukin-1; D018696:Neuroprotective Agents; D009574:Nitro Compounds; D011422:Propionates; D014409:Tumor Necrosis Factor-alpha; C015392:3-nitropropionic acid