Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Differential regulation of prostaglandin E biosynthesis by interferon-γ in colonic epithelial cells.
AU - Wright, Karen L.
AU - Weaver, Sean A.
AU - Patel, Kajal
AU - Coopman, Karen
AU - Feeney, Mark
AU - Kolios, George
AU - Robertson, Duncan A. F.
AU - Ward, Stephen G.
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
KW - Inflammation
KW - cyclooxygenase
KW - prostaglandin
KW - synthase
KW - cytokine
KW - colon
U2 - 10.1038/sj.bjp.0705719
DO - 10.1038/sj.bjp.0705719
M3 - Journal article
VL - 141
SP - 1091
EP - 1097
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 1476-5381
IS - 7
ER -