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

Wright, Karen L. and Weaver, Sean A. and Patel, Kajal and Coopman, Karen and Feeney, Mark and Kolios, George and Robertson, Duncan A. F. and Ward, Stephen G. (2004) Differential regulation of prostaglandin E biosynthesis by interferon-γ in colonic epithelial cells. British Journal of Pharmacology, 141 (7). pp. 1091-1097. ISSN 1476-5381

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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.

Item Type: Article
Journal or Publication Title: British Journal of Pharmacology
Uncontrolled Keywords: Inflammation ; cyclooxygenase ; prostaglandin ; synthase ; cytokine ; colon
Subjects: R Medicine > RM Therapeutics. Pharmacology
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 40892
Deposited By: Mr Richard Ingham
Deposited On: 16 Jun 2011 10:25
Refereed?: Yes
Published?: Published
Last Modified: 26 Jul 2012 18:06
Identification Number:
URI: http://eprints.lancs.ac.uk/id/eprint/40892

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