Levels of prostaglandin E metabolite and leukotriene E4 are increased in the urine of smokers: Evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway

Anna J. Duffield-Lillico, Jay O. Boyle, Kathy Zhou Xi, Aradhana Ghosh, Geera S. Butala, Kotha Subbaramaiah, Robert A. Newman, Jason D. Morrow, Ginger L. Milne, Andrew J. Dannenberg

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E4 (LTE4), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE4 were determined. Baseline levels of PGE-M and LTE4 were positively associated with smoking status; levels of PGE-M and LTE4 were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 ± 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE4, an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE4 were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE4 have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

Original languageEnglish (US)
Pages (from-to)322-329
Number of pages8
JournalCancer Prevention Research
Volume2
Issue number4
DOIs
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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