LOX activity and 13-HODE dehydrogenase in CECs were investigated after stimulation with arachidonic or linoleic acid. LOX metabolites were identified by RP-18 reversed-phase HPLC. Binding of 14C-labelled 13-Oxo-ODE was demonstrated using a His-tagged PPARγ.
Stimulation of HT-29 and primary CECs homogenates with and without Ca-ionophor was followed by the formation of high amounts of the linoleic acid metabolite 13-Oxo-ODE (155 and 85 ng/ml). The decrease of IL-8 secretion from IEC was more pronounced after pre-incubation with 13-Oxo-ODE compared to the PPARγ agonist troglitazone and higher as with the known PPARγ ligands 13-HODE and 15-HETE. Binding assays with 14C-labelled 13-Oxo-ODE clearly demonstrated a direct interaction.
High amounts of 13-Oxo-ODE can be induced in CECs by stimulation of linoleic acid metabolism. 13-Oxo-ODE binds to PPARγ and has anti-inflammatory effects. 13-HODE dehydrogenase might be a therapeutic target in IBD.