Interleukin-2 Suppresses Endothelin-1 Secretion of Cultured Endothelial Cells

The effect of recombinant interleukin-2 (IL-2) on endothelin-1 (ET-1) secretion was studied in bovine pulmonary arterial endothelial (BPAE) cells. IL-2 at concentrations of 1 to 10 U/ml significantly suppressed the basal secretion of ET-1 from BPAE cells. The maximal suppression, which was obtained with 1 U/ml of IL-2, was 74% of the control value during 24 h incubation. Moreover, incubation for 1 h with IL-2 at a concentration of 1 U/ml significantly lowered the prepro ET-1 mRNA level, measured by Northern blot analysis. Additions of 10^‒5 M of N^G-nitro-L-arginine, an inhibitor of nitric oxide (NO) synthesis, and of 10^‒5 M of methylene blue, an inhibitor of soluble guanylate cyclase, abolished the IL-2-induced suppression of ET-1 secretion. On the other hand, while addition of 10 U/ml of thrombin (TB) for 24 h significantly enhanced the secretion of ET-1 to about 128% of the control value, this enhancement was also inhibited by 100 U/ml of IL-2. IL-2 at more than 1 U/ml significantly increased the concentration of 6-keto-prostaglandin F_1α in the medium. However, addition of indomethacin (10^‒5 M) did not affect the IL-2-induced suppression of the basal ET-1 secretion, suggesting that prostaglandin I₂ does not participate in the IL-2-induced suppression. These findings indicate that IL-2 suppressed the synthesis of ET-1 at the mRNA transcription level, and that NO/cyclic GMP system enhanced by IL-2 in the endothelial cells may be responsible for IL-2-induced suppression of ET-1 synthesis. (Hypertens Res 1992; 15: 171-175).