Synergistic stimulation, by tumor necrosis factor-alpha and interferon-gamma, of fractalkine expression in human astrocytes

Fractalkine is a CX3C chemonkine that appears to be a neuron-to-microglia s ignal molecule in the central nervous system. We studied the expression of fractalkine in normal human astrocytes in culture, by using semi-quantitati ve reverse transcription-polymerase chain reaction and enzyme-linked immuno sorbent assay. We found that tumor-necrosis factor alpha (TNF-alpha) and in terferon-gamma (IFN-gamma) synergistically enhance the expression of fracta lkine. The expression of both fractalkine mRNA and protein was increased in time- and concentration-dependent manners in the cells co-stimulated with TNF-alpha and IFN-gamma. Cycloheximide, an inhibitor of protein synthesis, and dexamethasone had no effect on the synergy of the stimulation of fracta lkine expression. We conclude that normal human astrocytes produce fractalk ine by costimulation with pro-inflammatory cytokines and it may serve as a potential signal for immune and inflammatory responses in the central nervo us system. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.