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

Elizabeth J Bowen; Thomas W Schmidt; Christina S Firm; Andrew F Russo; Paul L Durham

doi:10.1111/j.1471-4159.2005.03524.x

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

Journal article

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

Elizabeth J Bowen, Thomas W Schmidt, Christina S Firm, Andrew F Russo and Paul L Durham

Journal of neurochemistry, Vol.96(1), pp.65-77

01/2006

DOI: 10.1111/j.1471-4159.2005.03524.x

PMCID: PMC1486866

PMID: 16277606

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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 factorα (TNFα). TNFR1 receptors were found on the majority of CGRP-containing rat trigeminal ganglion neurons. Treatment of cultures with TNFα stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNFα caused a coordinate increase in CGRP promoter activity. TNFα 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 TNFα 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.

mitogen-activated protein kinase

calcitonin gene-related peptide

cytokine, migraine

trigeminal

tumor necrosis factor-α

Details

Title: Subtitle: Tumor necrosis factor-α stimulation of calcitonin gene-related peptide expression and secretion from rat trigeminal ganglion neurons
Creators: Elizabeth J Bowen - Department of Biology, Missouri State University, Springfield, Missouri, USA
Thomas W Schmidt - Department of Physiology and Biophysics University of Iowa, Iowa City, Iowa, USA
Christina S Firm - Department of Genetics Program, University of Iowa, Iowa City, Iowa, USA
Andrew F Russo - Department of Physiology and Biophysics University of Iowa, Iowa City, Iowa, USA
Paul L Durham - Department of Biology, Missouri State University, Springfield, Missouri, USA
Resource Type: Journal article
Publication Details: Journal of neurochemistry, Vol.96(1), pp.65-77
DOI: 10.1111/j.1471-4159.2005.03524.x
PMID: 16277606
PMCID: PMC1486866
NLM abbreviation: J Neurochem
ISSN: 0022-3042
eISSN: 1471-4159
Language: English
Date published: 01/2006
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Internal Medicine
Record Identifier: 9984020610802771

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