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Extracellular ATP activates transcription factor NFAT in mouse microglial cells
Author(s) -
Ferrari Davide,
Stroh Christopher,
Wesselborg Sebastian,
Di Virgilio Francesco,
SchulzeOsthoff Klaus
Publication year - 2001
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.1118
Subject(s) - nfat , extracellular , calcineurin , microbiology and biotechnology , transcription factor , proinflammatory cytokine , biology , chemistry , biochemistry , transplantation , inflammation , medicine , immunology , gene
The effect of extracellular ATP on the activation of NFAT, an important transcription factor involved in cytokine expression, was investigated in the mouse microglial cell line N9. Incubation with ATP resulted in the potent and rapid activation of NFAT. Both NFAT1 and NFAT2 were activated by a calcineurin‐dependent pathway that required the influx of extracellular Ca 2+ . Inhibition of calcineurin by immunosuppressive drugs or Ca 2+ chelation prevented ATP‐induced activation and nuclear translocation of NFAT. Activation of NFAT by ATP involved a P2X 7 purinoreceptor‐mediated pathway. 2′,3′ ‐(4‐benzoyl)‐benzoyl‐ATP, an ATP analog with high affinity to the P2X 7 receptor, was a strong agonist of NFAT activation. In addition, microglial N9 clones selected for the absence of P2X 7 , but still expressing the P2Y subtype, revealed no NFAT activation in response to ATP, although NFAT could be still triggered by agents increasing intracellular Ca 2+ . Our data therefore suggest that triggering of the P2X 7 receptor by extracellular ATP is a potent mediator of transcription factor NFAT activation, and thus could be involved in early proinflammatory processes in the immune and nervous system. Drug Dev. Res. 52:213–219, 2001. © 2001 Wiley‐Liss, Inc.