Microglia-derived IGF-2 prevents TNFalpha induced death of mature oligodendrocytes in vitro.
Insulin-like growth factor-2 (IGF-2) present in media conditioned by non-activated and interferon gamma (IFN gamma)-treated microglia reduces galactocerebroside(+) (GalC) oligodendrocyte apoptosis in cultures derived both from the CG4 cell line and primary rat cortices. Microglia-derived IGF-2 also acts in each culture system to block GalC(+) oligodendrocyte toxicity resulting from soluble microglial-derived tumour necrosis factor alpha (TNF alpha). IGF-2 inhibits TNF alpha-induced c-Jun kinase (JNK) activation of the CG4 cell line. Microglial activation results in the release of soluble factors that are potentially toxic to oligodendrocytes but this may be offset by the production of soluble factors that protect these vulnerable cells. Allowing for extrapolation of these in vitro findings to intact tissue, our observations suggest one mechanism for limiting bystander damage in the context of inflammatory brain disease.
Nicholas
R S
RS
Neurology Unit, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK.
Stevens
S
S
Wing
M G
MG
Compston
D A
DA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005699:Galactosylceramides / Q000378:metabolism; D007328:Insulin / Q000502:physiology; D007335:Insulin-Like Growth Factor II / Q000276:immunology / Q000502:physiology*; D017628:Microglia / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000906:Antibodies; D017077:Culture Media, Conditioned; D005699:Galactosylceramides; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; C002454:galactocerebroside; D007335:Insulin-Like Growth Factor II; D020928:Mitogen-Activated Protein Kinases