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Differential regulation of prostaglandin E biosynthesis by interferon-γ in colonic epithelial cells.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Published
  • Karen L. Wright
  • Sean A. Weaver
  • Kajal Patel
  • Karen Coopman
  • Mark Feeney
  • George Kolios
  • Duncan A. F. Robertson
  • Stephen G. Ward
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<mark>Journal publication date</mark>04/2004
<mark>Journal</mark>British Journal of Pharmacology
Issue number7
Volume141
Number of pages7
Pages (from-to)1091-1097
Publication StatusPublished
<mark>Original language</mark>English

Abstract

Cyclooxygenase (COX)-2 expression and activity in response to pro-inflammatory cytokines TNFα and IFNγ was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549. TNFα induced concentration- and time-dependent upregulation of COX-2 mRNA, protein and prostaglandin (PG)E2 synthesis. Co-stimulation of TNFα with IFNγ resulted in reduced COX-2 mRNA and protein expression. IFNγ had no effect on the stability of TNFα-induced COX-2 mRNA. TNFα-induced PGE2 biosynthesis was significantly enhanced by the simultaneous addition of IFNγ and was COX-2 dependent. The combination of IFNγ and TNFα induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE2 synthesis. These results suggest that, in terms of PGE2 biosynthesis, IFNγ plays a negative regulatory role at the level of COX-2 expression and a positive regulatory role at the level of mPGES expression. This may have important implications for the clinical use of IFNγ in inflammatory diseases.