ACTIVATION OF THE PGE2 RECEPTOR EP4 PROTECTS AGAINST OXIDANT-INDUCED APOPTOSIS IN AIRWAY EPITHELIAL CELLS
Kalbfleisch, Emma R
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Heme oxygenase (HO)-1 expression is induced in pulmonary diseases characterized by oxidative stress, including CF, and is cytoprotective in nature. Prostaglanin (PG) E2 can protect against oxidant-induced apoptosis via upregulaton of HO-1 mediated via one of its receptor subtypes, EP2. Using model human airway epithelial cells, I have investigated whether pharmacological activation of PGE2 receptors (EP2 and EP4), induces HO-1 expression, and if so, can this protect the cells against oxidant-induced damage. EP2 and EP4 receptor activation had no significant effect on HO-1 expression, either at the gene or protein level; however, PGE2 itself and EP4 receptor activation protected against oxidant-induced apoptosis. EP2 receptor activation had no effect. Activation of neither receptor, nor PGE2, was effective at reducing H2O2-induced lipid peroxidation. Thus, while EP4 receptor activation is protective against oxidant-induced apoptosis in airway epithelial cells, this mechanism seems to be independent of HO-1 induction, and may reflect PGE2 production.