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 signal molecule in the central nervous system. We studied the expression of fractalkine in normal human astrocytes in culture, by using semi-quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. We found that tumor-necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) synergistically enhance the expression of fractalkine. 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 fractalkine expression. We conclude that normal human astrocytes produce fractalkine by co-stimulation with pro-inflammatory cytokines and it may serve as a potential signal for immune and inflammatory responses in the central nervous system.
Yoshida
H
H
Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu-cho, 036-8562, Hirosaki, Japan. hidemiyo@cc.hirosaki-u.ac.jp
Imaizumi
T
T
Fujimoto
K
K
Matsuo
N
N
Kimura
K
K
Cui
X
X
Matsumiya
T
T
Tanji
K
K
Shibata
T
T
Tamo
W
W
Kumagai
M
M
Satoh
K
K
D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics*; D004347:Drug Interactions / Q000502:physiology*; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D008565:Membrane Proteins / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology*
C515538:CX3CL1 protein, human; D018932:Chemokine CCL2; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma