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Differential regulation of prostaglandin E biosynthesis by interferon‐ γ in colonic epithelial cells
Author(s) -
Wright Karen L,
Weaver Sean A,
Patel Kajal,
Coopman Karen,
Feeney Mark,
Kolios George,
Robertson Duncan A F,
Ward Stephen G
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705719
Subject(s) - prostaglandin e , downregulation and upregulation , cyclooxygenase , prostaglandin , tumor necrosis factor alpha , prostaglandin e2 , cytokine , cell culture , stimulation , biosynthesis , messenger rna , chemistry , biology , medicine , endocrinology , enzyme , biochemistry , gene , genetics
Cyclooxygenase (COX)‐2 expression and activity in response to pro‐inflammatory cytokines TNF α and IFN γ was evaluated in the colonic epithelial cell line HT29 and the airway epithelial cell line A549. TNF α induced concentration‐ and time‐dependent upregulation of COX‐2 mRNA, protein and prostaglandin (PG)E 2 synthesis. Co‐stimulation of TNF α with IFN γ resulted in reduced COX‐2 mRNA and protein expression. IFN γ had no effect on the stability of TNF α ‐induced COX‐2 mRNA. TNF α ‐induced PGE 2 biosynthesis was significantly enhanced by the simultaneous addition of IFN γ and was COX‐2 dependent. The combination of IFN γ and TNF α induced the microsomal prostaglandin E synthase (mPGES), comensurate with the enhanced PGE 2 synthesis. These results suggest that, in terms of PGE 2 biosynthesis, IFN γ 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 γ in inflammatory diseases.British Journal of Pharmacology (2004) 141 , 1091–1097. doi: 10.1038/sj.bjp.0705719