Characterization of NF-kB-mediated inhibition ofcatechol-O-methyltransferase

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  • Tchivileva, Inna E.
    • Affiliation: School of Dentistry
    • Other Affiliation: Center for Neurosensory Disorders
  • Nackley, Andrea
    • Affiliation: School of Dentistry
    • Other Affiliation: Center for Neurosensory Disorders
  • Qian, Li
    • Affiliation: School of Dentistry
    • Other Affiliation: Comprehensive Center for Inflammatory Disorders
  • Wentworth, Sean
    • Affiliation: School of Dentistry
    • Other Affiliation: Center for Neurosensory Disorders
  • Conrad, Matthew
    • Affiliation: School of Dentistry
    • Other Affiliation: Center for Neurosensory Disorders
  • Diatchenko, Luda
    • Affiliation: School of Dentistry
    • Other Affiliation: Center for Neurosensory Disorders
Abstract
  • Abstract: Background: Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Specifically, low COMT activity is associated with heightened pain perception and development of musculoskeletal pain in humans as well as increased experimental pain sensitivity in rodents. Results: We report that the proinflammatory cytokine tumor necrosis factor α (TNFα) downregulates COMT mRNA and protein in astrocytes. Examination of the distal COMT promoter (P2-COMT) reveals a putative binding site for nuclear factor κB (NF-κB), the pivotal regulator of inflammation and the target of TNFα. Cell culture assays and functional deletion analyses of the cloned P2-COMT promoter demonstrate that TNFα inhibits P2-COMT activity in astrocytes by inducing NF-κB complex recruitment to the specific κB binding site. Conclusion: Collectively, our findings provide the first evidence for NF-κB-mediated inhibition of COMT expression in the central nervous system, suggesting that COMT contributes to the pathogenesis of inflammatory pain states.
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  • Article
Rights statement
  • In Copyright
Rights holder
  • Inna E Tchivileva et al.; licensee BioMed Central Ltd.
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Journal title
  • Molecular Pain
Journal volume
  • 5
Journal issue
  • 1
Page start
  • 13
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1744-8069
Bibliographic citation
  • Molecular Pain. 2009 Mar 16;5(1):13
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • August 23, 2012

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