COX inhibitors downregulate PDE4D expression in a clinical model of inflammatory pain.
Tumor necrosis factor-alpha (TNF-alpha) has a central role in inflammation and is modulated by prostaglandin E(2) (PGE(2)) and cyclic adenosine monophosphate (cAMP). Using microarray, quantitative real-time polymerase chain reaction (qRT-PCR), and protein detection techniques, we showed that ketorolac and rofecoxib had no significant effect on TNF-alpha gene expression in oral mucosal biopsies 3 h after surgery. They both, however, downregulated the gene and protein expression of phosphodiesterase type 4 (PDE4D), which might represent a novel mechanism contributing to their analgesic and anti-inflammatory effects.
Wang
X-M
XM
Pain Research Section, National Institute of Nursing Research, National Institutes of Health, Bethesda, Maryland, USA.
Hamza
M
M
Gordon
S M
SM
Wahl
S M
SM
Dionne
R A
RA
D000293:Adolescent; D000328:Adult; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000096:biosynthesis* / Q000235:genetics; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D010146:Pain / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D058987:Phosphodiesterase 3 Inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D016861:Cyclooxygenase Inhibitors; D058987:Phosphodiesterase 3 Inhibitors; D014409:Tumor Necrosis Factor-alpha; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517376:PDE4D protein, human