Molecular and cellular neurosciences
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Mol. Cell. Neurosci. · Jan 2008
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.
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. ⋯ 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.