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PIII‐4
Author(s) -
Wang X. M.,
Carmona G. N.,
Wu T. X.,
Kim H.,
Dionne R. A.
Publication year - 2006
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.2005.12.212
Subject(s) - rofecoxib , inflammation , medicine , chemokine , complement system , complement component 5 , ibuprofen , pharmacology , immunology , immune system , cyclooxygenase , biology , biochemistry , enzyme
BACKGROUND The regulation of the complement pathway by chemokines plays a key role in inflammation and pain. The study evaluated gene expression related to chemokines and complement components in a clinical model of inflammation and pain initiated by tissue injury, and following treatment by a selective or non‐selective COX‐2 inhibitor. METHODS Oral mucosal biopsies were taken prior to and 2 or 48 hrs post‐surgery from subjects undergoing tooth extraction, and received ibuprofen, rofecoxib or a placebo before surgery. Gene expression was analyzed on GEArray (n = 9) or Affymetrix microarray (n = 6). RESULTS Inflammation increased the gene expression of CCL2 (4‐fold, p = 0.01), CXCL2 (3‐fold, p = 0.01), and complement component C3 (2‐fold, p = 0.03) in 2 hrs post‐surgery tissues. In 48 hrs post‐surgery tissues, the gene expression of CCL2, CCL8, CCR1 and C3 was increased by 3‐fold (p = 0.09), 6‐fold (p = 0.03), 5‐fold (p = 0.01) and 14‐fold (p = 0.002), respectively. The up‐regulation of C3 was inhibited by rofecoxib (2‐fold decrease vs pre‐surgery, p = 0.38) and ibuprofen (7‐fold increase vs pre‐surgery, p = 0.05). The rofecoxib‐induced inhibition on C3 was different from that in placebo group (p = 0.02, Monte Carlo Estimation). CONCLUSIONS The results suggest that an association may exist between chemokines and complement activation at the transcriptional level during acute inflammation. The effects of rofecoxib on pain and inflammation may be associated with the suppression of C3 at the transcriptional level. Clinical Pharmacology & Therapeutics (2005) 79 , P58–P58; doi: 10.1016/j.clpt.2005.12.212