Modulation of Na⁺-Dependent Glutamate Transporter of Murine Astrocytes by Inflammatory Mediators

Abstract

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) E₂, interleukin (IL)-1βand IL-6 on Na⁺-dependent L-glutamate transport of astrocytes were analyzed using primary murine astrocytes. The exposure of astrocytes to PGE₂ 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 PGE₂-induced increase of L-glutamate uptake. IL-6 suppressed the increase of L-glutamate uptake induced by PGE₂. Kinetic analysis of L-glutamate uptake showed that PGE₂ and PGE₂ 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 PGE₂-induced V_max value. These results suggest that IL-1β, IL-6 and PGE₂ modulate glutamate transport of astrocytes and play a role in the pathogenesis of neurodegenerative disorders such as ALS and AD.