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- Title
Differential regulation of prostaglandin E biosynthesis by interferon-gamma in colonic epithelial cells.
- Authors
Wright, Karen L.; Weaver, Sean A.; Patel, Kajal; Coopman, Karen; Feeney, Mark; Kolios, George; Robertson, Duncan A.F.; Ward, Stephen G.
- Abstract
1. Cyclooxygenase (COX)-2 expression and activity in response to pro-inflammatory cytokines TNF alpha and IFN gamma was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549. 2. TNF alpha induced concentration- and time-dependent upregulation of COX-2 mRNA, protein and prostaglandin (PG)E(2) synthesis. 3. Co-stimulation of TNF alpha with IFN gamma resulted in reduced COX-2 mRNA and protein expression. 4. IFN gamma had no effect on the stability of TNF alpha-induced COX-2 mRNA. 5. TNF alpha-induced PGE(2) biosynthesis was significantly enhanced by the simultaneous addition of IFN gamma and was COX-2 dependent. 6. The combination of IFN gamma and TNF alpha induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE(2) synthesis. 7. These results suggest that, in terms of PGE(2) biosynthesis, IFN gamma 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 IFN gamma in inflammatory diseases.
- Subjects
INFLAMMATION; CYCLOOXYGENASES; PROSTAGLANDINS; CYTOKINES; COLON (Anatomy); EPITHELIAL cells; PROTEIN metabolism; RNA metabolism; ENZYME metabolism; ANIMAL experimentation; BIOCHEMISTRY; CELLS; COMBINATION drug therapy; COMPARATIVE studies; DOSE-effect relationship in pharmacology; ENZYME inhibitors; ENZYMES; INTERFERONS; PHENOMENOLOGY; RESEARCH methodology; MEDICAL cooperation; MICE; PROSTAGLANDINS E; PROTEINS; RESEARCH; RNA; TUMOR necrosis factors; EVALUATION research; DACTINOMYCIN; CHEMICAL inhibitors; PHARMACODYNAMICS
- Publication
British Journal of Pharmacology, 2004, Vol 141, Issue 7, p1091
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/sj.bjp.0705719