Mechanism of interleukin‐1β‐induced calcitonin gene‐related peptide production from dorsal root ganglion neurons of neonatal rats

Abstract

Calcitonin gene-related peptide (CGRP) is synthesized in dorsal root ganglion (DRG) neurons and released from primary afferent neurons to mediate hemodynamic effects and neurogenic inflammation. The effect of the proinflammatory cytokine interleukin-1 (IL-1)-β on CGRP release from these sensory neurons was investigated. The results showed that IL-1β (1 ng/ml) could directly induce CGRP release following prolonged incubation (24 hr) with these neurons. Treatment with IL-1β (0.1–1.0 ng/ml) significantly increased CGRP release in a concentration-dependent manner. In addition, pretreatment of DRG cells with actinomycin D at 1 μM or cyclohexamide at 10 μM for 30 min inhibited 1 ng/ml IL-1β-induced CGRP release in DRG neurons of neonatal rats. The inhibitors of PKC, JNK MAPK and NF-κB, but not p38 or ERK1/2 MAPK, blocked IL-1β-induced CGRP release. RNase protection assay showed that IL-1β could cause α-CGRP mRNA increase in a time- and concentration-dependent manner, although the level of β-CGRP mRNA was not affected. These results indicate that IL-1β may activate PKC, which in turn initiates JNK MAPK and activates NF-κB and finally induces α-CGRP gene expression and release from these sensory neurons.