Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells

Abstract

We have recently shown that the inflammatory process during experimental allergic encephalomyelitis (EAE), the animal model of MS, attracts transplanted NPC migration into the inflamed white matter. Here we studied how the proinflammatory cytokines tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ) affect NPC growth, survival, differentiation, and migration. Newborn rat striatal NPCs were expanded in spheres as nestin+, PSA-NCAM+, NG2(−) cells, which differentiated into astrocytes, oligodendrocytes, and neurons. NPCs expressed receptors of TNFα and IFNγ but not interleukin-1. TNFα and IFNγ inhibited sphere cell proliferation, determined by [3H]thymidine and BrdU incorporation. IFNγ increased apoptotic cell death (determined by TUNEL stains); this effect partially blocked by TNFα. Neither cytokine affected NPC lineage fate, determined by percentage of GFAP+, neurofilament+, and GalC+ cells after differentiation. TNFα and IFNγ increased outward migration of cells from spheres in vitro. Thus, TNFα and IFNγ, key players in MS and EAE, inhibit NPC proliferation and induce their migration.