P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways

Miho Shiratori, Hidetoshi Tozaki-Saitoh, Mai Yoshitake, Makoto Tsuda, Kazuhide Inoue

研究成果: Contribution to journalArticle査読

97 被引用数 (Scopus)

抄録

Microglia plays an important role in many neurodegenerative conditions. ATP leaked or released by damaged cells triggers microglial activation through P2 receptors, and stimulates the release of oxygen radicals, proinflammatory cytokines and chemokines from activated microglia. However, little is known about mechanisms underlying ATP-induced chemokine release from microglia. In this study, we found that a high concentration of ATP induces the mRNA expression and release of CXCL2 from microglia. A similar effect was observed following treatment of microglia with a P2X7 receptor (P2X7R) agonist, 2′-and 3′-O-(4-benzoylbenzoyl) ATP, and this was inhibited by pre-treatment with a P2X7R antagonist, Brilliant Blue G. ATP induced both activation of nuclear factor of activated T cells (NFAT) and MAPKs (p38, ERK, and JNK) through P2X7R. ATP-induced mRNA expression of CXCL2 was inhibited by INCA-6 (an NFAT inhibitor), SB203580 (a p38 inhibitor), U0126 (a MEK-ERK inhibitor) and JNK inhibitor II (a JNK inhibitor). However, MAPK inhibitors did not inhibit activation of NFAT. In addition, protein kinase C inhibitors suppressed ATP-induced ERK and JNK activation, and also inhibited ATP-induced CXCL2 expression in microglia. These results suggest that ATP increased CXCL2 production via both NFAT and protein kinase C/MAPK signaling pathways through P2X7 receptor stimulation in microglia.

本文言語英語
ページ(範囲)810-819
ページ数10
ジャーナルJournal of Neurochemistry
114
3
DOI
出版ステータス出版済み - 8 2010

All Science Journal Classification (ASJC) codes

  • 生化学
  • 細胞および分子神経科学

フィンガープリント

「P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル