Interleukin-13 upregulates vasodilatory 15-lipoxygenase eicosanoids in rabbit aorta.

OBJECTIVE Vasorelaxation of rabbit aorta is mediated by factors released from the vascular endothelium. In the aortic endothelium, arachidonic acid (AA) is metabolized via the 15-lipoxygenase pathway to the vasodilatory compounds 11,12,15-trihydroxyeicosatrienoic acid (THETA) and 15-hydroxy-11,12-epoxyeicosatrienoic acid (HEETA). Interleukin-13 (IL-13) increases 15-lipoxygenase expression and activity in several types of cells. We tested the hypothesis that IL-13 upregulates the 15-lipoxygenase pathway in rabbit aorta by inducing 15-lipoxygenase expression, thus increasing vascular relaxation mediated by THETA and HEETA. METHODS AND RESULTS Aorta rings and cultured endothelial cells were treated with IL-13, and 15-lipoxygenase expression was analyzed by reverse transcription-polymerase chain reaction and immunoblotting. 15-Lipoxygenase expression was increased by IL-13 in a concentration- and time-dependent manner. Aortic rings were incubated with [14C]AA, and the metabolites were extracted and resolved by high-performance liquid chromatography. IL-13 treatment increased the production of 15-hydroxyeicosatetraenoic acid, HEETA, and THETA. Indomethacin-resistant vasorelaxation to AA was significantly greater in IL-13-treated vessels than in controls. The relaxation responses to sodium nitroprusside were not altered by IL-13 treatment. CONCLUSIONS These data indicate that in the vascular endothelium, IL-13 induces the expression of 15-lipoxygenase and increases the production of the vasodilatory eicosanoids HEETA and THETA.