Characterization of NF-kB-mediated inhibition of catechol-<it>O</it>-methyltransferase
<p>Abstract</p> <p>Background</p> <p>Catechol-<it>O</it>-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 perceptio...
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| Main Authors: | , , , , , |
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| Format: | Book |
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SAGE Publishing,
2009-03-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | <p>Abstract</p> <p>Background</p> <p>Catechol-<it>O</it>-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.</p> <p>Results</p> <p>We report that the proinflammatory cytokine tumor necrosis factor α (TNFα) downregulates COMT mRNA and protein in astrocytes. Examination of the distal <it>COMT </it>promoter <it>(P2-COMT) </it>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 <it>P2-COMT </it>promoter demonstrate that TNFα inhibits <it>P2-COMT </it>activity in astrocytes by inducing NF-κB complex recruitment to the specific κB binding site.</p> <p>Conclusion</p> <p>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.</p> |
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| Item Description: | 10.1186/1744-8069-5-13 1744-8069 |