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Gene expression in the arachidonic acid pathway due to tissue injury and inflammation, an NSAID, and COXIB in a clinical model of pain
Author(s) -
Wang X. M.,
Wu T. X.,
Lee Y. S.,
Dionne R. A.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.034
Subject(s) - rofecoxib , ibuprofen , cyclooxygenase , medicine , inflammation , pharmacology , placebo , arachidonic acid , prostaglandin , anesthesia , pathology , chemistry , biochemistry , enzyme , alternative medicine
Background Acute inflammation is mediated by the arachidonic acid (AA) pathway with upregulation of cyclooxygenase (COX). This study evaluated gene expression initiated by tissue injury and inflammation in a clinical model of pain and its modulation by a selective COX‐2 inhibitor and a dual COX1/COX2 inhibitor. Methods Eighteen healthy volunteers randomly received ibuprofen, rofecoxib, or placebo before surgery. RNA was extracted from oral mucosal biopsies taken from the surgical site prior to tooth extraction and 48 hours post‐surgery. Labeled cRNA was hybridized onto Affymetric array (HG‐U133 plus 2.0). Data analysis was performed by ArrayAssist and permutation testing. Results In post‐surgery tissues in the placebo group, inflammation‐related genes, PTGIS, ALOX15 and GRIA4, were up‐regulated ≥ 3 fold from pre‐surgery baselines whereas these genes were down‐regulated or unchanged in the ibuprofen and rofecoxib groups. SOCS3, SOD2, and ANXA3, genes involved in inhibition of PLA2, were up‐regulated in the ibuprofen and rofecoxib groups. Genes related to prostaglandin activity, PSME3 and PTGFRN, were up‐regulated by rofecoxib. LOXE3, a gene in the lipoxygenases pathway, was down‐regulated in placebo and ibuprofen groups but unaffected by rofecoxib. Conclusions These results suggest that coxibs and NSAIDs result in differential effects on AA cascade gene expression following tissue injury which reflects the inhibition of COX by these drugs. Clinical Pharmacology & Therapeutics (2005) 77 , P8–P8; doi: 10.1016/j.clpt.2004.11.034