Effects of proinflammatory cytokines on the growth, fate, and motility of multipotential neural precursor cells.
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-alpha (TNFalpha) and interferon-gamma (IFNgamma) 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 TNFalpha and IFNgamma but not interleukin-1. TNFalpha and IFNgamma inhibited sphere cell proliferation, determined by [(3)H]thymidine and BrdU incorporation. IFNgamma increased apoptotic cell death (determined by TUNEL stains); this effect partially blocked by TNFalpha. Neither cytokine affected NPC lineage fate, determined by percentage of GFAP+, neurofilament+, and GalC+ cells after differentiation. TNFalpha and IFNgamma increased outward migration of cells from spheres in vitro. Thus, TNFalpha and IFNgamma, key players in MS and EAE, inhibit NPC proliferation and induce their migration.
Ben-Hur
Tamir
T
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Hospital, Jerusalem, Israel. tamir@hadassah.org.il
Ben-Menachem
Ofra
O
Furer
Victoria
V
Einstein
Ofira
O
Mizrachi-Kol
Rachel
R
Grigoriadis
Nikolaos
N
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D019070:Cell Lineage / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology; D018836:Inflammation Mediators / Q000276:immunology / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018874:Spheroids, Cellular; D013234:Stem Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma