Poly(I:C) promotes TNFa/TNFR1-dependent oligodendrocyte death in mixed glial cultures

Steelman, Andrew J; Li, Jianrong

To determine if preOL viability decreased upon poly (I:C) stimulation in various cultures we counted the number of preOLs under each condition. Consistent with the above data, stimulation of WT cultures with poly(I:C) or LPS resulted in significant loss of O4 + cells compared to vehicle control treated cultures (Figure 4B&4E ). In contrast, this cytotoxic effect was abolished in TNFα deficient mixed glial cultures ( Figure 4C ). Deletion of the TNFα receptor tnfr1 also abrogated the poly(I:C)-triggered TNF-mediated toxicity to preOLs ( Figure 4F ) despite a comparable level of TNFα production in WT and TNFR1 -/cultures (Figure 4D) . These results demonstrate that TNFα is required for oligodendroglial cell death in mixed cultures challenged with poly(I:C) or LPS and that the signal needed to induce cell death is dependent on TNFR1.