Tumor necrosis factor-α stimulation of calcitonin gene-related peptide expression and secretion from rat trigeminal ganglion neurons

Authors

Elizabeth J. Bowen, Missouri State University
Thomas W. Schmidt
Christina S. Firm
Andrew F. Russo
Paul L. Durham, Missouri State UniversityFollow

Abstract

Expression of the neuropeptide calcitonin gene-related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factor-α (TNF-α). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNF-α stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNF-α caused a coordinate increase in CGRP promoter activity. TNF-α treatment activated the transcription factor NF-κB, as well as the Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways. The importance of TNF-α induction of MAP kinase pathways was demonstrated by inhibiting MAP kinases with pharmacological reagents and gene transfer with an adenoviral vector encoding MAP kinase phosphatase-1 (MKP-1). We propose that selective and regulated inhibition of MAP kinases in trigeminal neurons may be therapeutically beneficial for inflammatory disorders involving elevated CGRP levels.

Department(s)

Biology

Document Type

Article

DOI

https://doi.org/10.1111/j.1471-4159.2005.03524.x

Keywords

Calcitonin gene-related peptide, Cytokine, Migraine, Mitogen-activated protein kinase, Trigeminal, Tumor necrosis factor-α

Publication Date

1-1-2006

Recommended Citation

Bowen, Elizabeth J., Thomas W. Schmidt, Christina S. Firm, Andrew F. Russo, and Paul L. Durham. "Tumor necrosis factor‐α stimulation of calcitonin gene‐related peptide expression and secretion from rat trigeminal ganglion neurons." Journal of neurochemistry 96, no. 1 (2006): 65-77.

Journal Title

Journal of Neurochemistry