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

Abstract

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.