Mechanism of interleukin-1 beta-induced calcitonin gene-related peptide production from dorsal root ganglion neurons of neonatal rats.
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)-beta on CGRP release from these sensory neurons was investigated. The results showed that IL-1beta (1 ng/ml) could directly induce CGRP release following prolonged incubation (24 hr) with these neurons. Treatment with IL-1beta (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 microM or cyclohexamide at 10 microM for 30 min inhibited 1 ng/ml IL-1beta-induced CGRP release in DRG neurons of neonatal rats. The inhibitors of PKC, JNK MAPK and NF-kappaB, but not p38 or ERK1/2 MAPK, blocked IL-1beta-induced CGRP release. RNase protection assay showed that IL-1beta could cause alpha-CGRP mRNA increase in a time- and concentration-dependent manner, although the level of beta-CGRP mRNA was not affected. These results indicate that IL-1beta may activate PKC, which in turn initiates JNK MAPK and activates NF-kappaB and finally induces alpha-CGRP gene expression and release from these sensory neurons.
Hou
Lingfei
L
Institute of Vascular Medicine, Peking University Third Hospital, Peking University, Beijing, People's Republic of China.
Li
Wenjing
W
Wang
Xian
X
D000818:Animals; D000831:Animals, Newborn; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007375:Interleukin-1; D015740:Calcitonin Gene-Related Peptide