Activation of the nuclear factor of activated T-cells (NFAT) mediates upregulation of CCR2 chemokine receptors in dorsal root ganglion (DRG) neurons: A possible mechanism for activity-dependent transcription in DRG neurons in association with neuropathic pain

Hosung Jung, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Upregulation of CCR2 chemokine receptor expression by dorsal root ganglion (DRG) neurons is an important process in the development and maintenance of neuropathic pain. CCR2 is not expressed by DRG neurons under normal conditions but is upregulated in several animal models of neuropathic pain where its signaling is excitatory. However, the molecular mechanisms underlying neuronal upregulation of CCR2 have not been investigated. We examined the promoter region of the CCR2 gene and found that a binding site for the nuclear factor of activated T-cells (NFAT) was conserved among species. The NFAT element was functional since the CCR2 promoter was activated by a constitutively active form of calcineurin A, whereas a point mutation in the NFAT binding site abrogated it. Activation of the NFAT pathway in the DRG neuronal cell line F11 increased CCR2 promoter activity and induced CCR2 transcription. Moreover, depolarization of cultured DRG neurons induced de novo synthesis of CCR2 mRNA, which was blocked by the calcineurin inhibitors cyclosporin A and FK506. These data indicate that CCR2 is a target of the NFAT pathway and suggest that tonic excitation of DRG neurons in association with chronic pain may lead to neuronal CCR2 upregulation via activation of the NFAT pathway.

Original languageEnglish (US)
Pages (from-to)170-177
Number of pages8
JournalMolecular and Cellular Neuroscience
Volume37
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Calcineurin
  • Chemokine receptors
  • Cyclosporin A
  • Dorsal root ganglion
  • FK506
  • NFAT
  • Neuropathic pain

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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