TY - JOUR
T1 - Tumor necrosis factor-α and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture
AU - Liu, Yu Peng
AU - Lin, Hsin I.
AU - Tzeng, Shun Fen
N1 - Funding Information:
This study was supported by grants from the National Science Council, Taiwan (NSC912311B006004 and NSC922218E006024).
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/8/30
Y1 - 2005/8/30
N2 - Neural progenitor cells (NPCs) in developing and adult CNS are capable of giving rise to various neuronal and glial cell populations. Neurogenesis in the adult hippocampus has been found to be inhibited by a proinflammatory cytokine, interleukin-6 (IL-6), suggesting that activated microglia in the inflamed brain may control neurogenesis. Yet, little is known about the effect of microglia-derived factors on the cell fate of embryonic NPCs. In this study, we show that neurons with βIII-tubulin immunoreactivity in the NPC culture were reduced by the condition media collected from microglia treated with endotoxin lipopolysaccharide (LPS/M-CM). Treatment with pentoxifylline (PTX), an inhibitor for tumor necrosis factor-α (TNF-α) secretion from LPS-activated microglia, blocked the reduction of βIII-tubulin+ cells in NPC culture. Furthermore, treatment of NPCs with interleukin-18 (IL-18), a recently discovered proinflammatory cytokine, also decreased the number of βIII-tubulin+ cells in a dose- and time-dependent manner. Surprisingly, we also observed that the remaining βIII-tubulin + cells in the LPS/M-CM-treated culture exhibited more branching neurites. Thus, the activated microglia-derived cytokines, TNF-α and IL-18, may either inhibit the neuronal differentiation or induce neuronal cell death in the NPC culture, whereas these cells may also produce factors to improve the neurite branching in the NPC culture.
AB - Neural progenitor cells (NPCs) in developing and adult CNS are capable of giving rise to various neuronal and glial cell populations. Neurogenesis in the adult hippocampus has been found to be inhibited by a proinflammatory cytokine, interleukin-6 (IL-6), suggesting that activated microglia in the inflamed brain may control neurogenesis. Yet, little is known about the effect of microglia-derived factors on the cell fate of embryonic NPCs. In this study, we show that neurons with βIII-tubulin immunoreactivity in the NPC culture were reduced by the condition media collected from microglia treated with endotoxin lipopolysaccharide (LPS/M-CM). Treatment with pentoxifylline (PTX), an inhibitor for tumor necrosis factor-α (TNF-α) secretion from LPS-activated microglia, blocked the reduction of βIII-tubulin+ cells in NPC culture. Furthermore, treatment of NPCs with interleukin-18 (IL-18), a recently discovered proinflammatory cytokine, also decreased the number of βIII-tubulin+ cells in a dose- and time-dependent manner. Surprisingly, we also observed that the remaining βIII-tubulin + cells in the LPS/M-CM-treated culture exhibited more branching neurites. Thus, the activated microglia-derived cytokines, TNF-α and IL-18, may either inhibit the neuronal differentiation or induce neuronal cell death in the NPC culture, whereas these cells may also produce factors to improve the neurite branching in the NPC culture.
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U2 - 10.1016/j.brainres.2005.06.085
DO - 10.1016/j.brainres.2005.06.085
M3 - Article
C2 - 16054598
AN - SCOPUS:24044485264
VL - 1054
SP - 152
EP - 158
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 2
ER -