Sodium-dependent glutamate transporters of astrocytes have been reported to maintain extracellular concentration of glutamate below toxic level in the central nervous system and to be concerned with neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). In this study, the effects of inflammatory mediators including prostaglandin (PG) E
2, interleukin (IL)-1βand IL-6 on Na
+-dependent L-glutamate transport of astrocytes were analyzed using primary murine astrocytes. The exposure of astrocytes to PGE
2 for 24h elicited a dose-dependent increase of L-glutamate uptake. Neither IL-1β nor IL-6 alone had any effect on L-glutamate uptake. However, IL-1β enhanced the PGE
2-induced increase of L-glutamate uptake. IL-6 suppressed the increase of L-glutamate uptake induced by PGE
2. Kinetic analysis of L-glutamate uptake showed that PGE
2 and PGE
2 with IL-1β increased V
max value with no significant effect on K
m value for Na
+-dependent L-glutamate uptake. IL-6 suppressed the PGE
2-induced V
max value. These results suggest that IL-1β, IL-6 and PGE
2 modulate glutamate transport of astrocytes and play a role in the pathogenesis of neurodegenerative disorders such as ALS and AD.
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