RGD Reference Report - Role of prostaglandin E2 in the synthesis of the pro-inflammatory cytokine interleukin-6 in primary sensory neurons: an in vivo and in vitro study. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Role of prostaglandin E2 in the synthesis of the pro-inflammatory cytokine interleukin-6 in primary sensory neurons: an in vivo and in vitro study.

Authors: St-Jacques, B  Ma, W 
Citation: St-Jacques B and Ma W, J Neurochem. 2011 Sep;118(5):841-54. doi: 10.1111/j.1471-4159.2011.07230.x. Epub 2011 Mar 28.
RGD ID: 6483537
Pubmed: PMID:21371033   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1471-4159.2011.07230.x   (Journal Full-text)

Following various types of nerve injury, cyclooxygenase 2 and prostaglandin E2 (PGE2) are universally and chronically up-regulated in injured nerves and contribute to the genesis of neuropathic pain. Persistent high levels of PGE2 likely exert chronic effects on nociceptive dorsal root ganglion (DRG) neurons. In the present study, we tested the hypothesis that injured nerve-derived PGE2 contributes to the up-regulation of the pro-inflammatory cytokine interleukin-6 (IL-6) in DRG neurons following partial sciatic nerve ligation. In naive adult rats, IL-6 was expressed in only a few small size DRG neurons which all co-expressed EP4 receptors. Partial sciatic nerve ligation increased and shifted IL-6 expression from small to medium and large size damaged DRG neurons. Perineural injection of a selective cyclooxygenase 2 inhibitor or a selective EP4 receptor antagonist significantly suppressed the up-regulation of IL-6 in DRG, suggesting that injured nerve derived PGE2 contributes to the de novo synthesis of IL-6 in DRG neurons through EP4 receptors. In cultured sensory ganglion explants, a stabilized PGE2 analog increased IL-6 mRNA and protein levels through the activation of EP4, protein kinase A, protein kinase C, extracellular regulated protein kinase/MAPK, cAMP response element binding protein and NFkappaB signalling pathways. Taken together, these data indicate that facilitating the de novo synthesis of pain-related cytokines in injured medium and large size DRG neurons is a novel mechanism underlying the role of injured nerve derived PGE2 in the genesis of neuropathic pain.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Nociceptive Pain  ISO (All species)6483537; 6483537 RGD 
Nociceptive Pain  IMP 6483537 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptger4  (prostaglandin E receptor 4)

Genes (Mus musculus)
Ptger4  (prostaglandin E receptor 4 (subtype EP4))

Genes (Homo sapiens)
PTGER4  (prostaglandin E receptor 4)


Additional Information