Microglia-derived IGF-2 prevents TNF alpha induced death of mature oligodendrocytes in vitro

Insulin-like growth factor-2 (IGF-2) present in media conditioned by non-activated and interferon gamma (IFNgamma)-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 (TNFalpha). IGF-2 inhibits TNFalpha-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. (C) 2002 Elsevier Science B.V. All rights reserved.