TY - JOUR
T1 - Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells
AU - Ben-Hur, Tamir
AU - Ben-Menachem, Ofra
AU - Furer, Victoria
AU - Einstein, Ofira
AU - Mizrachi-Kol, Rachel
AU - Grigoriadis, Nikolaos
N1 - Funding Information:
This study was supported by The Israel Science Foundation (Grant 481/99) and in part by the Hilda Katz Blaustein Fund for Research in Neurology and the Lena P. Harvey Endowment Fund for Neurological Research. We thank S. Rotshenker for his helpful suggestions.
PY - 2003/11
Y1 - 2003/11
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0344737625
U2 - 10.1016/S1044-7431(03)00218-5
DO - 10.1016/S1044-7431(03)00218-5
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C2 - 14664813
AN - SCOPUS:0344737625
SN - 1044-7431
VL - 24
SP - 623
EP - 631
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 3
ER -